{
	"616": {"label": 2, "data": {"text": "Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed phorbol 12-myristate 13-acetate plus ionomycin-induced IL-2 secretion in a concentration-dependent manner.", "entity1": "IL-2", "entity2": "phorbol 12-myristate 13-acetate", "span1": [124, 128], "span2": [69, 100]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10214": {"label": 2, "data": {"text": "We recently reported that AMPK is activated by metformin in cultured rat hepatocytes, mediating the inhibitory effects of the drug on hepatic glucose production.", "entity1": "AMPK", "entity2": "metformin", "span1": [26, 30], "span2": [47, 56]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"11127": {"label": 1, "data": {"text": "Prazosin was found to be unselective; 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), 5-methyl-urapidil, indoramin and (+)-niguldipine were confirmed as selective for the alpha 1A-adrenoceptor, whereas spiperone was weakly alpha 1B-selective.", "entity1": "alpha 1A-adrenoceptor", "entity2": "WB 4101", "span1": [192, 213], "span2": [97, 104]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9744": {"label": 4, "data": {"text": "In [(35)S]GTPgammaS binding protocols, yohimbine exerts antagonist actions at halpha(2A)-AR, h5-HT(1B), h5-HT(1D), and hD(2) sites, yet partial agonist actions at h5-HT(1A) sites.", "entity1": "h5-HT(1A)", "entity2": "yohimbine", "span1": [163, 172], "span2": [39, 48]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8013": {"label": 3, "data": {"text": "In addition, treatment with IMG and hyperoside resulted in inhibition of TNF-\u03b1-induced production of PAI-1, and treatment with IMG resulted in significant reduction of the PAI-1 to t-PA ratio.", "entity1": "TNF-\u03b1", "entity2": "IMG", "span1": [73, 78], "span2": [28, 31]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"14533": {"label": 1, "data": {"text": "ColQ-1a is expressed at the neuromuscular junction (NMJ) in fast-twitch muscle, and this expression depends on trophic factors supplied by motor neurons signaling via a cAMP-dependent pathway in muscle.", "entity1": "ColQ-1a", "entity2": "cAMP", "span1": [0, 7], "span2": [169, 173]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10415": {"label": 2, "data": {"text": "RESULTS: Rolipram unmasked the inhibitory effect of beta(2)-adrenoceptor stimulation with salmeterol and significantly attenuated the stimulated release of AA and subsequent LTC(4).", "entity1": "beta(2)-adrenoceptor", "entity2": "salmeterol", "span1": [52, 72], "span2": [90, 100]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"86": {"label": 1, "data": {"text": "The high-affinity of catecholamines to phenylalanine hydroxylase is a valuable probe to study the active site of this enzyme and is also relevant for the homologous enzyme tyrosine hydroxylase, which is purified as a stable catecholamine-Fe(III) complex.", "entity1": "tyrosine hydroxylase", "entity2": "catecholamines", "span1": [172, 192], "span2": [21, 35]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11261": {"label": 0, "data": {"text": "D-Serine was previously identified in mammalian brain and was shown to be a co-agonist at the 'glycine' site of the N-methyl-D-aspartate (NMDA)-type receptors.", "entity1": "N-methyl-D-aspartate (NMDA)-type receptors", "entity2": "glycine", "span1": [116, 158], "span2": [95, 102]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14984": {"label": 2, "data": {"text": "Additionally, these effects of ATO on \u03b3-H2AX, Chk1, Chk2, p53, and p21(waf1/cip1) were reduced by an ATM inhibitor.", "entity1": "waf1", "entity2": "ATO", "span1": [71, 75], "span2": [31, 34]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3249": {"label": 1, "data": {"text": "Here, translocation studies using the human androgen receptor (hAR) and the human glucocorticoid receptor (hGR) were performed to aid in identifying the mechanism by which anabolic-androgenic steroids (AAS) were activating hAR and potentially interacting with hGR and how glucocorticoid ligands were interacting with the hGR and hAR.", "entity1": "hGR", "entity2": "steroids", "span1": [260, 263], "span2": [192, 200]}, "weak_labels": [-1, -1, -1, -1, 1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11636": {"label": 1, "data": {"text": "In this report, we demonstrate the utility of reversed-phase protein chromatography and FT-ICR mass spectrometry in analyzing CCNU (lomustine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitroso-urea, MW: 233.7Da) modification of stathmin.", "entity1": "stathmin", "entity2": "1-(2-chloroethyl)-3-cyclohexyl-1-nitroso-urea", "span1": [219, 227], "span2": [143, 188]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2496": {"label": 3, "data": {"text": "Licofelone, a dual anti-inflammatory drug that inhibits 5-lipoxygenase (LOX) and cyclooxygenase (COX) enzymes, may have a better cardiovascular profile that cycloxygenase-2 inhibitors due to cycloxygenase-1 blockade-mediated antithrombotic effect and a better gastrointestinal tolerability.", "entity1": "LOX", "entity2": "Licofelone", "span1": [72, 75], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11470": {"label": 8, "data": {"text": "Rats were fed experimental diets containing SPI or casein as a nitrogen source.", "entity1": "casein", "entity2": "nitrogen", "span1": [51, 57], "span2": [63, 71]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8612": {"label": 2, "data": {"text": "Besides this direct activity, an excess of phenolic compounds detectable in red wine, may exert an additional indirect action by blocking oxysterol-related NOX1 induction, thus totally preventing the pro-oxidant and pro-inflammatory events triggered by dietary oxysterols.", "entity1": "NOX1", "entity2": "oxysterol", "span1": [156, 160], "span2": [138, 147]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2378": {"label": 3, "data": {"text": "Further characterization of sorafenib revealed that this molecule was a multikinase inhibitor that targeted the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-beta and Kit), which play key roles in tumor progression and angiogenesis.", "entity1": "VEGFR-2", "entity2": "sorafenib", "span1": [164, 171], "span2": [28, 37]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"967": {"label": 3, "data": {"text": "U50, 488H caused a significant down-regulation of the hkor, although etorphine did not.", "entity1": "hkor", "entity2": "U50, 488H", "span1": [54, 58], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"236": {"label": 1, "data": {"text": "In all cases at both the 5-HT2A and 5-HT2C receptors, the affinities of the isomers of MDMA and MDA were at least 2-3 orders of magnitude less than 5-HT.", "entity1": "5-HT2C", "entity2": "MDMA", "span1": [36, 42], "span2": [87, 91]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15855": {"label": 8, "data": {"text": "These results suggest that ABCA1 actively eliminates 24-OHC in the presence of HDL as a lipid acceptor and protects neuronal cells.", "entity1": "ABCA1", "entity2": "24-OHC", "span1": [27, 32], "span2": [53, 59]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6112": {"label": 3, "data": {"text": "The results when considered with previous reports in the literature show that amezinium is about 1000 times more potent and debrisoquine is about 20 times more potent for MAO inhibition in rat lungs than in tissue homogenates, and the reason for their high potencies in the intact lungs is transport and accumulation of the drugs in the pulmonary endothelial cells by uptake1.", "entity1": "MAO", "entity2": "debrisoquine", "span1": [171, 174], "span2": [124, 136]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"13773": {"label": 3, "data": {"text": "Others kinase inhibitors used recently in cancer therapy include Dasatinib (BMS-354825) specific for ABL non-receptor cytoplasmic kinase, Gefitinib (Iressa), Erlotinib (OSI-774, Tarceva) and Sunitinib (SU 11248, Sutent) specific for VEGF receptor kinase, AMN107 (Nilotinib) and INNO-406 (NS-187) specific for c-KIT kinase.", "entity1": "c-KIT", "entity2": "Nilotinib", "span1": [309, 314], "span2": [263, 272]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6507": {"label": 3, "data": {"text": "UNLABELLED: Rabeprazole is an inhibitor of the gastric proton pump.", "entity1": "gastric proton pump", "entity2": "Rabeprazole", "span1": [47, 66], "span2": [12, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7989": {"label": 2, "data": {"text": "ISO significantly inhibited the levels of ERK1/2 kinase and increased the expression of JNK and p38 kinases.", "entity1": "p38", "entity2": "ISO", "span1": [96, 99], "span2": [0, 3]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12371": {"label": 8, "data": {"text": "A., Ventura, F. V., Houten, S. M. Carnitine palmitoyltransferase 2 and carnitine/acylcarnitine translocase are involved in the mitochondrial synthesis and export of acylcarnitines.", "entity1": "carnitine/acylcarnitine translocase", "entity2": "acylcarnitines", "span1": [71, 106], "span2": [165, 179]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8300": {"label": 1, "data": {"text": "Autophagy takes place in mutated p53 neuroblastoma cells in response to hypoxia mimetic CoCl(2).", "entity1": "p53", "entity2": "CoCl(2)", "span1": [33, 36], "span2": [88, 95]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6728": {"label": 3, "data": {"text": "Compounds of several other structural families, including the quinoxaline AG1296, the bis(1H-2-indolyl)-1-methanone D-65476, the indolinones SU5416 and SU11248, the indolocarbazoles PKC412 and CEP-701, and the piperazonyl quinazoline CT53518, are potent inhibitors of Flt3 kinase.", "entity1": "Flt3", "entity2": "SU5416", "span1": [268, 272], "span2": [141, 147]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"876": {"label": 8, "data": {"text": "Inhibition of S-adenosylmethionine decarboxylase by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of spermidine and spermine with a significant accumulation of putrescine and induction of ODC.", "entity1": "S-adenosylmethionine decarboxylase", "entity2": "spermine", "span1": [14, 48], "span2": [154, 162]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10111": {"label": 3, "data": {"text": "Cyclooxygenase-1 (COX-1) inhibitors (flurbiprofen, ketoprofen and ketrolack) attenuated the nicotine-induced contraction in a concentration-dependent manner, and cyclooxygenase-2 (COX-2) inhibitors at high concentrations (nimesulide and NS-389) slightly attenuated the contraction.", "entity1": "Cyclooxygenase-1", "entity2": "flurbiprofen", "span1": [0, 16], "span2": [37, 49]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13420": {"label": 8, "data": {"text": "Furthermore, the enzymatic activity of alanine aminotransferase (ALT), which converts the critical gluconeogenic amino acid alanine into pyruvate, is decreased (approximately 50%) in KLF15-/- hepatocytes.", "entity1": "ALT", "entity2": "amino acid", "span1": [65, 68], "span2": [113, 123]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, 9]},
	"2569": {"label": 3, "data": {"text": "Brain tissue analyses revealed that neonatal quinpirole treatment produced a significant decrease in hippocampal NGF, BDNF and ChAT that was eliminated by olanzapine treatment.", "entity1": "NGF", "entity2": "quinpirole", "span1": [113, 116], "span2": [45, 55]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"3951": {"label": 1, "data": {"text": "Rufinamide attenuates mechanical allodynia in a model of neuropathic pain in the mouse and stabilizes voltage-gated sodium channel inactivated state.", "entity1": "voltage-gated sodium channel", "entity2": "Rufinamide", "span1": [102, 130], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15874": {"label": 3, "data": {"text": "The selective CaMKII\u03b1 inhibitor KN-62 reversed the blockade produced by ionomycin and K(+)-depolarization.", "entity1": "CaMKII\u03b1", "entity2": "ionomycin", "span1": [14, 21], "span2": [72, 81]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"10842": {"label": 3, "data": {"text": "Imatinib (STI571, Gleevec, Glivec; Novartis Pharmaceuticals, East Hanover, NJ), a selective inhibitor of KIT, ABL, BCR-ABL, PDGFRA, and PDGFRB, represents a new paradigm of targeted cancer therapy and has revolutionized the treatment of patients with chronic myelogenous leukemia and GISTs.", "entity1": "PDGFRA", "entity2": "STI571", "span1": [124, 130], "span2": [10, 16]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8439": {"label": 2, "data": {"text": "HENA activated the BK (cbv1 + \u03b21) channels cloned from rat cerebral artery myocytes with a potency (EC50 = 53 \u03bcM) similar to and an efficacy (\u00d72.5 potentiation) significantly greater than that of LCA.", "entity1": "BK (cbv1 + \u03b21) channels", "entity2": "HENA", "span1": [19, 42], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9261": {"label": 3, "data": {"text": "Ergot alkaloids were also effective in inhibiting VIP-stimulated cyclic AMP production, with EC50 values for ergovaline, ergonovine, alpha-ergocryptine, ergotamine, and dopamine of 8 +/- 2, 47 +/- 2, 28 +/- 2, 2 +/- 1, and 8 +/- 1 nM, respectively.", "entity1": "VIP", "entity2": "alpha-ergocryptine", "span1": [50, 53], "span2": [133, 151]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"11280": {"label": 8, "data": {"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with glycine (Gly) as one-carbon (1-C) source.", "entity1": "glycine decarboxylase complex", "entity2": "Gly", "span1": [80, 109], "span2": [198, 201]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10470": {"label": 5, "data": {"text": "Pretreatment with a combination of (+/-)-2-hydroxy-5-[2-[[2-hydroxy-3-[4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2 -yl]phenoxy]propyl]amino]ethoxy]-benzamide methanesulfonate (CGP20712A, a selective beta(1)-adrenoceptor antagonist) and (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-buta nol hydrochloride (ICI-118,5511, a selective beta(2)-adrenoceptor antagonist) (0.1 microM for each) produced a 14-fold rightward shift of the concentration-response curve for (-)-isoprenaline; however, the relaxation in response to (+/-)-CGP12177A was unaffected by the blockade of beta(1)- and beta(2)-adrenoceptors.", "entity1": "beta(1)-adrenoceptor", "entity2": "(+/-)-2-hydroxy-5-[2-[[2-hydroxy-3-[4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2 -yl]phenoxy]propyl]amino]ethoxy]-benzamide methanesulfonate", "span1": [201, 221], "span2": [35, 176]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"2270": {"label": 8, "data": {"text": "Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released glutamate and its conversion to glutamine through the enzyme glutamine synthetase (GS).", "entity1": "glutamine synthetase", "entity2": "glutamate", "span1": [175, 195], "span2": [114, 123]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1]},
	"273": {"label": 3, "data": {"text": "The channel activators avermectin and moxidectin usually retain their inhibitory potency in the Rdl subunit mutants.", "entity1": "Rdl", "entity2": "avermectin", "span1": [96, 99], "span2": [23, 33]}, "weak_labels": [-1, -1, 0, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10761": {"label": 2, "data": {"text": "Imatinib-induced changes were blocked with the EGFR antagonist cetuximab, which suggested direct involvement of EGFR in this process.", "entity1": "EGFR", "entity2": "Imatinib", "span1": [112, 116], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13815": {"label": 3, "data": {"text": "Others kinase inhibitors used recently in cancer therapy include Dasatinib (BMS-354825) specific for ABL non-receptor cytoplasmic kinase, Gefitinib (Iressa), Erlotinib (OSI-774, Tarceva) and Sunitinib (SU 11248, Sutent) specific for VEGF receptor kinase, AMN107 (Nilotinib) and INNO-406 (NS-187) specific for c-KIT kinase.", "entity1": "kinase", "entity2": "OSI-774", "span1": [247, 253], "span2": [169, 176]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"475": {"label": 1, "data": {"text": "In functional experiments, risperidone is selective, not for the B, but for the A subtype of alpha 1-adrenoceptors.", "entity1": "alpha 1-adrenoceptors", "entity2": "risperidone", "span1": [93, 114], "span2": [27, 38]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9728": {"label": 0, "data": {"text": "Substitutions for Ile(183)-Val(191) and Ser(195)-Ile(197) at the N terminus and for Ser(258)-Ser(264) at the C terminus of the A3 domain markedly decreased factor XI coagulant activity.", "entity1": "A3 domain", "entity2": "C", "span1": [127, 136], "span2": [109, 110]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7706": {"label": 2, "data": {"text": "atropine, AChE reactivator such as one of the recommended pyridinium oximes (pralidoxime, trimedoxime, obidoxime and HI-6) and diazepam are used for the treatment of OP poisoning in humans.", "entity1": "AChE", "entity2": "pralidoxime", "span1": [10, 14], "span2": [77, 88]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11631": {"label": 3, "data": {"text": "Ex vivo IC(50) values (COX-1: 105.2 micromol/L; COX-2: 26.3 micromol/L) of acetaminophen compared favorably with its in vitro IC(50) values.", "entity1": "COX-2", "entity2": "acetaminophen", "span1": [48, 53], "span2": [75, 88]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5781": {"label": 3, "data": {"text": "Inhibition of binding of both plasminogen and plasmin to gp330 by benzamidine was similar, although EACA inhibited the binding of plasmin to gp330 slightly more than the binding of plasminogen to gp330.", "entity1": "plasminogen", "entity2": "benzamidine", "span1": [30, 41], "span2": [66, 77]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4190": {"label": 2, "data": {"text": "PTE also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.", "entity1": "Bak", "entity2": "PTE", "span1": [205, 208], "span2": [0, 3]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14217": {"label": 6, "data": {"text": "The structurally diverse opioids codeine and eseroline, like galantamine, are also nAChR-APL that have greatly diminished affinity for AChE, representing potential lead compounds for selective nAChR-APL development.", "entity1": "nAChR", "entity2": "galantamine", "span1": [83, 88], "span2": [61, 72]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1567": {"label": 8, "data": {"text": "One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to oxoglutaramic acid (GTK, EC 2.6.1.15).", "entity1": "GTK", "entity2": "oxoglutaramic acid", "span1": [176, 179], "span2": [156, 174]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, 8, -1, 9]},
	"1315": {"label": 1, "data": {"text": "A novel SCN5A arrhythmia mutation, M1766L, with expression defect rescued by mexiletine.", "entity1": "M1766L", "entity2": "mexiletine", "span1": [35, 41], "span2": [77, 87]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11833": {"label": 1, "data": {"text": "However, NCFP provides greater mGlu5 subtype selectivity than does CPPHA, making it more suitable for studies of effects on mGlu5 in CNS preparations.", "entity1": "mGlu5", "entity2": "CPPHA", "span1": [31, 36], "span2": [67, 72]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13102": {"label": 4, "data": {"text": "Glinides, sulfonylureas, and other acidified sulfonamides may be promising leads in the development of new PPARgamma agonists.", "entity1": "PPARgamma", "entity2": "acidified sulfonamides", "span1": [107, 116], "span2": [35, 57]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2511": {"label": 3, "data": {"text": "IRF3 activation induced by MyD88-independent signaling components, TRIF and TBK1, was also downregulated by auranofin.", "entity1": "TRIF", "entity2": "auranofin", "span1": [67, 71], "span2": [108, 117]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3020": {"label": 3, "data": {"text": "Statins are 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors broadly used for the control of hypercholesterolemia.", "entity1": "3-hydroxy-3-methylglutaryl-CoA reductase", "entity2": "Statins", "span1": [12, 52], "span2": [0, 7]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9953": {"label": 9, "data": {"text": "Selective COX-2 inhibitors, such as meloxicam, celecoxib (SC-58635), and rofecoxib (MK-0966), are NSAIDs that have been modified chemically to preferentially inhibit COX-2 but not COX-1.", "entity1": "COX-1", "entity2": "rofecoxib", "span1": [180, 185], "span2": [73, 82]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"5034": {"label": 5, "data": {"text": "Synthesis and in Vitro Characterisation of Ifenprodil-Based Fluorescein Conjugates as GluN1/GluN2B N-Methyl-D-aspartate Receptor Antagonists.", "entity1": "N-Methyl-D-aspartate Receptor", "entity2": "Fluorescein", "span1": [99, 128], "span2": [60, 71]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8689": {"label": 3, "data": {"text": "Thus, imatinib and other c-Abl kinase inhibitors provide an intriguing new way to halt cisplatin-induced oocyte death in early follicles and perhaps conserve the endocrine function of the ovary against chemotherapy.Cell Death and Differentiation advance online publication, 19 April 2013; doi:10.1038/cdd.2013.31.", "entity1": "c-Abl", "entity2": "imatinib", "span1": [25, 30], "span2": [6, 14]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7877": {"label": 3, "data": {"text": "Antiretroviral protease inhibitors lopinavir (LPV) and ritonavir (RTV) are reported BSEP inhibitors.", "entity1": "protease", "entity2": "lopinavir", "span1": [15, 23], "span2": [35, 44]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10869": {"label": 5, "data": {"text": "Moreover, 4-methylhistamine potently activated the hH(4)R (pEC(50) = 7.4 +/- 0.1; alpha = 1), and this response was competitively antagonized by the selective H(4)R antagonist JNJ 7777120 [1-[(5-chloro-1H-indol-2-yl)-carbonyl]-4-methylpiperazine] (pA(2) = 7.8).", "entity1": "H(4)R", "entity2": "1-[(5-chloro-1H-indol-2-yl)-carbonyl]-4-methylpiperazine", "span1": [159, 164], "span2": [189, 245]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4155": {"label": 3, "data": {"text": "Pharmacokinetic and pharmacodynamic modeling of hedgehog inhibitor TAK-441 for the inhibition of Gli1 messenger RNA expression and antitumor efficacy in xenografted tumor model mice.", "entity1": "Gli1", "entity2": "TAK-441", "span1": [97, 101], "span2": [67, 74]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9638": {"label": 3, "data": {"text": "Down-regulation of prostate-specific antigen (PSA) expression, an AR-target gene, by estramustine and bicalutamide was accompanied by the blockade of the mutated androgen receptor.", "entity1": "prostate-specific antigen", "entity2": "bicalutamide", "span1": [19, 44], "span2": [102, 114]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8769": {"label": 5, "data": {"text": "Of note, SB265610 which is a close structural analogue of SB225002 with a potent IL-8RB antagonistic activity did not exhibit a similar antimitotic activity.", "entity1": "IL-8RB", "entity2": "SB225002", "span1": [81, 87], "span2": [58, 66]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7925": {"label": 8, "data": {"text": "In conclusion, rCtr1 can transport copper and platinum drugs, and sensitizes cells to their cytotoxicities.", "entity1": "rCtr1", "entity2": "copper", "span1": [15, 20], "span2": [35, 41]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"10758": {"label": 1, "data": {"text": "Together, these results suggested that imatinib affects EGFR activation and signaling pathways through rapid release and increased expression of endogenous EGFR-activating ligands.", "entity1": "EGFR", "entity2": "imatinib", "span1": [56, 60], "span2": [39, 47]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13643": {"label": 1, "data": {"text": "Top1p is the cellular target of the anti-cancer drug camptothecin (CPT), which reversibly stabilizes a covalent enzyme-DNA intermediate.", "entity1": "Top1p", "entity2": "CPT", "span1": [0, 5], "span2": [67, 70]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2462": {"label": 9, "data": {"text": "The adenosine triphosphate binding cassette (ABC)-transporter ABCC2 (MRP2/cMOAT) can mediate resistance against the commonly used anticancer drugs cisplatin and paclitaxel.", "entity1": "cMOAT", "entity2": "paclitaxel", "span1": [74, 79], "span2": [161, 171]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"11861": {"label": 1, "data": {"text": "We examined the effects of anthocyanidins (cyanidin, delphinidin, malvidin, peonidin, petunidin, pelargonidin) on the aryl hydrocarbon receptor (AhR)-CYP1A1 signaling pathway in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cells.", "entity1": "AhR", "entity2": "cyanidin", "span1": [145, 148], "span2": [43, 51]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12930": {"label": 8, "data": {"text": "Hydrogen sulfide (H(2)S), a regulatory gaseous molecule that is endogenously synthesized by cystathionine gamma-lyase (CSE) and/or cystathionine beta-synthase (CBS) from L-cysteine (L-Cys) metabolism, is a putative vasodilator, and its role in nitric oxide (NO) production is unexplored.", "entity1": "CSE", "entity2": "L-Cys", "span1": [119, 122], "span2": [182, 187]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"7159": {"label": 2, "data": {"text": "CONCLUSION: Our data provides a novel insight into an effect of telmisartan: telmisartan inhibits AT1R gene expression through PPARgamma activation.", "entity1": "PPARgamma", "entity2": "telmisartan", "span1": [127, 136], "span2": [77, 88]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6368": {"label": 4, "data": {"text": "The related piperidines ohmefentanyl and sufentanil and the nonselective opioid receptor agonist etorphine were less potent nociceptin receptor agonists.", "entity1": "nociceptin receptor", "entity2": "etorphine", "span1": [124, 143], "span2": [97, 106]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7031": {"label": 1, "data": {"text": "Further, cholesterol metabolites, predominantly the oxysterols, the natural ligands for liver X receptor (LXR), induced these genes via upregulation of sterol regulatory element binding protein-1c (SREBP-1c) that bound to the regulatory regions of these genes.", "entity1": "LXR", "entity2": "oxysterols", "span1": [106, 109], "span2": [52, 62]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1949": {"label": 1, "data": {"text": "These results demonstrate that this receptor corresponds to the previously called \"P2t\" platelet receptor and show that the active metabolite of clopidogrel binds in a covalent manner to this receptor, thus explaining how it blocks the aggregating effect of ADP on platelets.", "entity1": "platelet receptor", "entity2": "clopidogrel", "span1": [88, 105], "span2": [145, 156]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4497": {"label": 9, "data": {"text": "Valproate-\u03b2-d-glucuronide and CGP 47292-\u03b2-d-glucuronide did not inhibit either hCES.", "entity1": "hCES", "entity2": "Valproate-\u03b2-d-glucuronide", "span1": [79, 83], "span2": [0, 25]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"11583": {"label": 2, "data": {"text": "As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved HbA(1c) to a significantly greater extent than placebo when added to metformin or pioglitazone and was noninferior to glipizide when added to metformin.", "entity1": "HbA(1c)", "entity2": "metformin", "span1": [128, 135], "span2": [197, 206]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4727": {"label": 3, "data": {"text": "In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of TCDD on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "entity1": "Wnt", "entity2": "TCDD", "span1": [59, 62], "span2": [34, 38]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, 3, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"13223": {"label": 9, "data": {"text": "Here we report that glutamate stimulation caused a rapid reduction in protein levels of GRIP1, but not that of glutamate receptor (GluR) 1, GluR2 and protein interacting with C kinase 1 (PICK1) in rat primary cortical neuron cultures.", "entity1": "protein interacting with C kinase 1", "entity2": "glutamate", "span1": [150, 185], "span2": [20, 29]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, 2, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9781": {"label": 4, "data": {"text": "These studies provide compelling evidence that the antitussive effects of SB 227122 in this guinea pig cough model are mediated by agonist activity at the delta-opioid receptor.", "entity1": "delta-opioid receptor", "entity2": "SB 227122", "span1": [155, 176], "span2": [74, 83]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6766": {"label": 2, "data": {"text": "Hydralazine induced rapid and transient expression of HIF-1alpha and downstream targets of HIF (endothelin-1, adrenomedullin, haem oxygenase 1, and vascular endothelial growth factor [VEGF]) in endothelial and smooth muscle cells and induced endothelial cell-specific proliferation.", "entity1": "HIF", "entity2": "Hydralazine", "span1": [91, 94], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"271": {"label": 1, "data": {"text": "The non-competitive blocker site of the GABA-gated chloride ion channel in normal susceptible strains of Drosophila melanogaster and simulans binds 4-n-[3H]propyl-4'-ethynylbicycloorthobenzoate ([3H]EBOB) at specific sites with KdS of 1.6-1.9 nM and BmaxS of 171-181 fmol/mg protein.", "entity1": "GABA-gated chloride ion channel", "entity2": "[3H]EBOB", "span1": [40, 71], "span2": [195, 203]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10872": {"label": 1, "data": {"text": "Late-onset diarrhea appears to be associated with intestinal exposure to SN-38 (7-ethyl-10-hydroxycamptothecin), the major active metabolite of CPT-11, which may bind to Topo I and induce apoptosis of intestinal epithelia, leading to the disturbance in the absorptive and secretory functions of mucosa.", "entity1": "Topo I", "entity2": "CPT-11", "span1": [170, 176], "span2": [144, 150]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6631": {"label": 1, "data": {"text": "5TFI was incorporated into a model target protein, murine dihydrofolate reductase (mDHFR), in an isoleucine auxotrophic Escherichia coli host strain suspended in 5TFI-supplemented minimal medium depleted of isoleucine.", "entity1": "mDHFR", "entity2": "5TFI", "span1": [83, 88], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5086": {"label": 3, "data": {"text": "FCEO significantly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) by suppressing the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, respectively.", "entity1": "cyclooxygenase (COX)-2", "entity2": "PGE2", "span1": [159, 181], "span2": [69, 73]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7639": {"label": 3, "data": {"text": "We found compounds that inhibited Panx1 currents with a rank order of potency: carbenoxolone > disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) approximately disodium 4-acetamido-4'-isothiocyanato-stilben-2,2'-disulfonate approximately 5-nitro-2-(3-phenylpropylamino)benzoic acid > indanyloxyacetic acid 94 >> probenecid >> flufenamic acid = niflumic acid.", "entity1": "Panx1", "entity2": "DIDS", "span1": [34, 39], "span2": [152, 156]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11945": {"label": 8, "data": {"text": "The CYP2B6*6 Allele Significantly Alters the N-demethylation of Ketamine Enantiomers In Vitro.", "entity1": "CYP2B6*6", "entity2": "Ketamine", "span1": [4, 12], "span2": [64, 72]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12265": {"label": 0, "data": {"text": "Identification of N-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function.", "entity1": "adrenomedullin", "entity2": "N", "span1": [121, 135], "span2": [18, 19]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11757": {"label": 0, "data": {"text": "Results demonstrate that predominantly FUT7, and to a lesser extent FUT4, forms the selectin-ligand at the N terminus of leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) in humans and mice.", "entity1": "P-selectin glycoprotein ligand-1", "entity2": "N", "span1": [131, 163], "span2": [107, 108]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6689": {"label": 2, "data": {"text": "TRPM8 (CMR1) is a Ca(2+)-permeable channel, which can be activated by low temperatures, menthol, eucalyptol and icilin.", "entity1": "CMR1", "entity2": "menthol", "span1": [7, 11], "span2": [88, 95]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11158": {"label": 8, "data": {"text": "Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A).", "entity1": "human phosphodiesterase", "entity2": "cAMP", "span1": [40, 63], "span2": [85, 89]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1746": {"label": 4, "data": {"text": "Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the beta(2)-adrenoceptor agonist formoterol [eformoterol].", "entity1": "beta(2)-adrenoceptor", "entity2": "formoterol", "span1": [92, 112], "span2": [121, 131]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14294": {"label": 3, "data": {"text": "In utero exposure to valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, causes neural tube, heart, and limb defects.", "entity1": "histone deacetylase", "entity2": "valproic acid", "span1": [44, 63], "span2": [21, 34]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11023": {"label": 3, "data": {"text": "Comparison of captopril and enalapril to study the role of the sulfhydryl-group in improvement of endothelial dysfunction with ACE inhibitors in high dieted methionine mice.", "entity1": "ACE", "entity2": "enalapril", "span1": [127, 130], "span2": [28, 37]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6558": {"label": 3, "data": {"text": "In contrast, the mutants T844A, F972A and Q975A showed increased K(i) for cilostazol but no difference for milrinone from the recombinant PDE3A.", "entity1": "T844A", "entity2": "milrinone", "span1": [25, 30], "span2": [107, 116]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1568": {"label": 8, "data": {"text": "One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to oxoglutaramic acid (GTK, EC 2.6.1.15).", "entity1": "EC 2.6.1.15", "entity2": "oxoglutaramic acid", "span1": [181, 192], "span2": [156, 174]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, 8, -1, 9]},
	"867": {"label": 3, "data": {"text": "Inhibition of S-adenosylmethionine decarboxylase by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of spermidine and spermine with a significant accumulation of putrescine and induction of ODC.", "entity1": "S-adenosylmethionine decarboxylase", "entity2": "diethylglyoxal bis-(guanylhydrazone)", "span1": [14, 48], "span2": [74, 110]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12340": {"label": 9, "data": {"text": "In contrast, flunisolide was only metabolized via CYP3A4, with no significant turnover by CYP3A5 or CYP3A7.", "entity1": "CYP3A5", "entity2": "flunisolide", "span1": [90, 96], "span2": [13, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9370": {"label": 3, "data": {"text": "Binding of thalidomide to alpha1-acid glycoprotein may be involved in its inhibition of tumor necrosis factor alpha production.", "entity1": "tumor necrosis factor alpha", "entity2": "thalidomide", "span1": [88, 115], "span2": [11, 22]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"9080": {"label": 2, "data": {"text": "The order of effect was 4HPR greater than ROAc greater than 13cisRA, with increases in prothrombin times correlating with increases in hemorrhagic deaths.", "entity1": "prothrombin", "entity2": "4HPR", "span1": [87, 98], "span2": [24, 28]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7221": {"label": 1, "data": {"text": "Since the GnRH receptor has been shown to affect sex steroid hormone receptor function, we considered that part of GnRH analog actions on prostate cells may be mediated through modulation of the human androgen receptor.", "entity1": "human androgen receptor", "entity2": "GnRH", "span1": [195, 218], "span2": [115, 119]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11433": {"label": 1, "data": {"text": "In the presence of alphaAR blockade, concentration-response curves for isoproterenol, norepinephrine, and epinephrine suggested that a beta1AR was involved in this response, and the rank order of potency was isoproterenol > norepinephrine = epinephrine.", "entity1": "beta1AR", "entity2": "epinephrine", "span1": [135, 142], "span2": [241, 252]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12816": {"label": 3, "data": {"text": "Treatment with carvedilol is associated with a reversal of abnormal regulation of HIF-1alpha, VEGF, BNP, and NGF-beta in the hypertrophic myocardium.", "entity1": "HIF-1alpha", "entity2": "carvedilol", "span1": [82, 92], "span2": [15, 25]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14012": {"label": 3, "data": {"text": "Treatment with cabozantinib inhibited MET and VEGFR2 phosphorylation in vitro and in tumor models in vivo and led to significant reductions in cell invasion in vitro.", "entity1": "VEGFR2", "entity2": "cabozantinib", "span1": [46, 52], "span2": [15, 27]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1374": {"label": 1, "data": {"text": "The L0 linker has been reported to be required for glibenclamide binding, and DeltaNK(IR)6.2/SUR1 channels exhibit reduced labeling of K(IR) with (125)I-azidoglibenclamide, implying that the K(IR) N terminus and L0 of SUR1 are in proximity.", "entity1": "K(IR)", "entity2": "(125)I-azidoglibenclamide", "span1": [135, 140], "span2": [146, 171]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6866": {"label": 9, "data": {"text": "In contrast, caspase-8 activation and Bid truncation triggered by Jo2 were not diminished by minocycline pretreatment in mouse livers.", "entity1": "caspase-8", "entity2": "minocycline", "span1": [13, 22], "span2": [93, 104]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"189": {"label": 1, "data": {"text": "Readdition of a small quantity of dialyzed serum to cytosol preparations yielded a profile of steroid binding similar to that of the kidney mineralocorticoid receptor (aldosterone greater than desoxycorticosterone greater than corticosterone).", "entity1": "mineralocorticoid receptor", "entity2": "aldosterone", "span1": [140, 166], "span2": [168, 179]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10483": {"label": 4, "data": {"text": "The aim of this study was, therefore, to provide comparative binding characteristics of agonists (epinephrine, norepinephrine, isoproterenol, fenoterol, salbutamol, salmeterol, terbutalin, formoterol, broxaterol) and antagonists (propranolol, alprenolol, atenolol, metoprolol, bisoprolol, carvedilol, pindolol, BRL 37344, CGP 20712, SR 59230A, CGP 12177, ICI 118551) at all three subtypes of human beta-adrenergic receptors in an identical cellular background.", "entity1": "human beta-adrenergic receptors", "entity2": "salbutamol", "span1": [392, 423], "span2": [153, 163]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1999": {"label": 0, "data": {"text": "Furthermore, a combinatory mutation (Pro(7.31)-Pro(7.32)-Ser(7.33) motif to Ser-Glu-Pro in EL3 and Leu(7.38), Leu(7.43), Ala(7.46), and Pro(7.47) to those of rat GnRHR) in gmGnRH-2 exhibited an approximately 500-fold increased sensitivity to GnRH-I, indicating that these residues are critical for discriminating GnRH-II from GnRH-I.", "entity1": "rat GnRHR", "entity2": "Leu", "span1": [158, 167], "span2": [110, 113]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8713": {"label": 2, "data": {"text": "The mRNA levels of SOD1, CAT, GPx and Txnrd1 were increased significantly (P<0.05) in the combined Na2SeO3+NaAsO2 treatment group.", "entity1": "SOD1", "entity2": "Na2SeO3", "span1": [19, 23], "span2": [99, 106]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8099": {"label": 2, "data": {"text": "Wogonin inhibits H2O2-induced vascular permeability through suppressing the phosphorylation of caveolin-1.", "entity1": "caveolin-1", "entity2": "H2O2", "span1": [95, 105], "span2": [17, 21]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12736": {"label": 3, "data": {"text": "Agents which have recently been shown to block cyclin D1 translation by regulating calcium levels are the unsaturated essential fatty acid, eicosapentaenoic acid (EPA), the antidiabetic thiazolidinediones, and the antifungal agent, clotrimazole.", "entity1": "cyclin D1", "entity2": "clotrimazole", "span1": [47, 56], "span2": [232, 244]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12772": {"label": 1, "data": {"text": "Thymidylate synthase (TS) continues to be a critical target for 5-fluorouracil (5-FU) and its prodrugs, UFT/LV (Orzel), capecitabine (Xeloda), and S-1, primarily because this enzyme is essential for the synthesis of 2-deoxythymidine-5-monophosphate, a precursor for DNA synthesis.", "entity1": "TS", "entity2": "UFT", "span1": [22, 24], "span2": [104, 107]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12624": {"label": 1, "data": {"text": "The EP1 receptor bound 17-phenyl-PGE2, sulprostone and iloprost in addition to PGE2 and PGE1, with Ki values of 14-36 nM.", "entity1": "EP1", "entity2": "sulprostone", "span1": [4, 7], "span2": [39, 50]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4752": {"label": 3, "data": {"text": "In cultured vascular smooth muscle cells (VSMCs), rAAV-mediated CYP2J2 overexpression and EETs markedly suppressed Ang II-induced inflammatory cytokine expression.", "entity1": "cytokine", "entity2": "EETs", "span1": [143, 151], "span2": [90, 94]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14535": {"label": 3, "data": {"text": "Data at transcriptional level also demonstrated that catalpol potently attenuated gene expressions involved in inflammation, such as iNOS, COX-2 and TLR4.", "entity1": "COX-2", "entity2": "catalpol", "span1": [139, 144], "span2": [53, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10898": {"label": 1, "data": {"text": "Pyridoxal kinase (PDXK) catalyzes the phosphorylation of pyridoxal, pyridoxamine, and pyridoxine in the presence of ATP and Zn2+.", "entity1": "PDXK", "entity2": "Zn2+", "span1": [18, 22], "span2": [124, 128]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"3127": {"label": 1, "data": {"text": "The neuronal vesicular monoamine transporter (VMAT2) is the target molecule of action of some psychostimulants, such as methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA).", "entity1": "neuronal vesicular monoamine transporter", "entity2": "methamphetamine", "span1": [4, 44], "span2": [120, 135]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"9918": {"label": 1, "data": {"text": "These results do not support previous results of altered [3H]paroxetine binding sites in alcohol-dependent subjects or 5-HTTLPR S-allele carriers.", "entity1": "5-HTTLPR", "entity2": "[3H]paroxetine", "span1": [119, 127], "span2": [57, 71]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3049": {"label": 8, "data": {"text": "PGE(2) is synthesized from arachidonic acid by cyclooxygenases (COX) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4).", "entity1": "prostaglandin E synthases", "entity2": "arachidonic acid", "span1": [73, 98], "span2": [27, 43]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2280": {"label": 1, "data": {"text": "In addition to this evidence (for the involvement of EP2 receptors), evidence for the involvement of EP1 receptors in the PGE1 mediated stimulation of Na,K-ATPase beta subunit gene transcription includes the stimulatory effect of 17-phenyl trinor PGE2, as well as the inhibitory effects of SC-51089.", "entity1": "EP1 receptors", "entity2": "PGE1", "span1": [101, 114], "span2": [122, 126]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3512": {"label": 8, "data": {"text": "Aldo-keto reductases (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.", "entity1": "Aldo-keto reductases", "entity2": "o-quinones", "span1": [0, 20], "span2": [142, 152]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"7794": {"label": 3, "data": {"text": "We examined in cats the 1) ulcerogenic effects of selective COX-1 (SC-560, ketorolac) and COX-2 (celecoxib, meloxicam) inhibitors on the gastrointestinal mucosa, 2) effect of feeding and cimetidine on the expression of COX isoforms and prostaglandin E(2) (PGE(2)) level in the duodenum, and 3) localization of COX isoforms in the duodenum.", "entity1": "COX-2", "entity2": "meloxicam", "span1": [90, 95], "span2": [108, 117]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14179": {"label": 0, "data": {"text": "CBDP irreversibly inhibits butyrylcholinesterase (BChE) in human plasma by forming adducts on the active site serine (Ser-198).", "entity1": "butyrylcholinesterase", "entity2": "serine", "span1": [27, 48], "span2": [110, 116]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13881": {"label": 3, "data": {"text": "The molecular mechanisms by which ibuprofen inhibits the RhoA signal in neurons, however, remain unclear.", "entity1": "RhoA", "entity2": "ibuprofen", "span1": [57, 61], "span2": [34, 43]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"676": {"label": 8, "data": {"text": "Of the PDE inhibitors tested, dipyridamole was most effective, with IC50 values of 1.2 and 0.45 microM for inhibition of cAMP and cGMP hydrolysis, respectively.", "entity1": "PDE", "entity2": "cAMP", "span1": [7, 10], "span2": [121, 125]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"508": {"label": 3, "data": {"text": "The results suggest that the 63-kDa (PDE 1B1) and 60-kDa (PDE 1A2) CaMPDE isozymes are inhibited by felodipine and nicardipine by partial competitive inhibition and that these two Ca2+ antagonists appear to counteract each other.", "entity1": "CaMPDE", "entity2": "nicardipine", "span1": [67, 73], "span2": [115, 126]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12525": {"label": 1, "data": {"text": "For all retinoid-dosed groups maintained on the purified diet, changes in prothrombin times occured as early as 1 week.", "entity1": "prothrombin", "entity2": "retinoid", "span1": [74, 85], "span2": [8, 16]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1187": {"label": 4, "data": {"text": "Bovine tracheal smooth muscle strips were incubated with 10 microM fenoterol or vehicle for various periods of time (5, 30 min, 18 h) at 37 degrees C. After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial muscarinic receptor agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and histamine.", "entity1": "muscarinic receptor", "entity2": "histamine", "span1": [299, 318], "span2": [402, 411]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1776": {"label": 2, "data": {"text": "CGP 12177A but not isoprenaline initiated arrhythmias at lower concentrations following beta(1)-adrenoceptor overexpression.", "entity1": "beta(1)-adrenoceptor", "entity2": "CGP 12177A", "span1": [88, 108], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9234": {"label": 8, "data": {"text": "The holo activity of AGT 2 with a high Km for L-alanine decreased more slowly than AGT 1 (by 33% in 14 days, by 60% in 28 days).", "entity1": "AGT 1", "entity2": "L-alanine", "span1": [83, 88], "span2": [46, 55]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10643": {"label": 1, "data": {"text": "The overall saturation binding affinity for COX-2 of valdecoxib is 2.6 nM (compared with 1.6 nM for celecoxib, 51 nM for rofecoxib, and 260 nM for etoricoxib), with a slow off-rate (t(1/2) approximately 98 min).", "entity1": "COX-2", "entity2": "valdecoxib", "span1": [44, 49], "span2": [53, 63]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7624": {"label": 8, "data": {"text": "Lapatinib is metabolized primarily by the cytochrome P450 3A4 isozyme, with 1 metabolite remaining active against EGFR but not HER2.", "entity1": "cytochrome P450 3A4", "entity2": "Lapatinib", "span1": [42, 61], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"16026": {"label": 1, "data": {"text": "Administration of haloperidol increased Ser240/244 phosphorylation in a subpopulation of GABA-ergic medium spiny neurons (MSNs), which express dopamine D2 receptors (D2Rs).", "entity1": "dopamine D2 receptors", "entity2": "haloperidol", "span1": [143, 164], "span2": [18, 29]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15048": {"label": 1, "data": {"text": "The contrasting activity of iodido versus chlorido ruthenium and osmium arene azo- and imino-pyridine anticancer complexes: control of cell selectivity, cross-resistance, p53 dependence, and apoptosis pathway.", "entity1": "p53", "entity2": "chlorido ruthenium", "span1": [171, 174], "span2": [42, 60]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"208": {"label": 3, "data": {"text": "Alprenolol and BAAM at 10(-7), 3 x 10(-7), and 10(-6) M inhibited the cardiac stimulation response slightly, which is indicative of membrane-stabilizing activity independent of beta-adrenoceptor blockade.", "entity1": "beta-adrenoceptor", "entity2": "BAAM", "span1": [177, 194], "span2": [15, 19]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11918": {"label": 1, "data": {"text": "We studied accumulation of lipid metabolites [triglycerides (TAGs), diglycerides (DAGs)] and ceramides in relation to insulin signaling and expression and phosphorylation of PTP1B by preincubating rat skeletal muscle cells (L6 myotubes) with three saturated and three unsaturated free fatty acids (FFAs) (200 \u03bcM).", "entity1": "PTP1B", "entity2": "DAGs", "span1": [174, 179], "span2": [82, 86]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8697": {"label": 8, "data": {"text": "Among the possible transporters involved in the uptake of Cd(2+) and Mn(2+), the expression of ZIP8 (Zrt-, Irt-related protein 8), encoded by Slc39a8, showed a marked suppression in both RBL-Cdr and RBL-Mnr cells.", "entity1": "Zrt-, Irt-related protein 8", "entity2": "Mn(2+)", "span1": [101, 128], "span2": [69, 75]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"9788": {"label": 5, "data": {"text": "In contrast, combined pretreatment with beta-funaltrexamine (mu-receptor antagonist; 20 mg/kg, s.c.) and norbinaltorphimine (kappa-receptor antagonist; 20 mg/kg, s.c.), at doses that inhibited the antitussive activity of mu- and kappa-receptor agonists, respectively, was without effect on the antitussive response of SB 227122 (20 mg/kg, i.p.).", "entity1": "kappa-receptor", "entity2": "norbinaltorphimine", "span1": [125, 139], "span2": [105, 123]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1293": {"label": 8, "data": {"text": "BACKGROUND AND AIMS: Glutamic acid decarboxylase (GAD, EC 4.1.1.15) catalyses the conversion of glutamate to gamma-aminobutyric acid (GABA).", "entity1": "EC 4.1.1.15", "entity2": "GABA", "span1": [55, 66], "span2": [134, 138]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 8, -1]},
	"13644": {"label": 1, "data": {"text": "The physical connection of the linker with the Top1p clamp as well as linker flexibility affect enzyme sensitivity to CPT.", "entity1": "Top1p", "entity2": "CPT", "span1": [47, 52], "span2": [118, 121]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15126": {"label": 3, "data": {"text": "Notably, the antioxidant Trolox\u2122 reversed the Mn (20\u00a0mg/kg)-dependent augmentation in p38(MAPK) phosphorylation and reduced the Mn (20\u00a0mg/kg)-induced caspase activity and F(2)-isoprostane production.", "entity1": "MAPK", "entity2": "Trolox", "span1": [90, 94], "span2": [25, 31]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 9]},
	"11767": {"label": 0, "data": {"text": "Incubation of purified Pin1 with HNE followed by MALDI-TOF/TOF mass spectrometry resulted in detection of Michael adducts at the active site residues His-157 and Cys-113.", "entity1": "Pin1", "entity2": "His", "span1": [23, 27], "span2": [150, 153]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13045": {"label": 8, "data": {"text": "Here we demonstrate that PPARgamma, turns on retinoic acid synthesis by inducing the expression of retinol and retinal metabolizing enzymes such as retinol dehydrogenase 10 and retinaldehyde dehydrogenase type 2 (RALDH2).", "entity1": "retinol dehydrogenase 10", "entity2": "retinol", "span1": [148, 172], "span2": [99, 106]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"664": {"label": 3, "data": {"text": "METHODS: COX-1 inhibition was determined by measuring thromboxane B2 (TXB2)-generation from clotting whole blood ex vivo after single oral doses of 7.5 and 15 mg meloxicam and 75 mg diclofenac and at steady state (15 mg meloxicam daily and 150 mg diclofenac daily).", "entity1": "COX-1", "entity2": "diclofenac", "span1": [9, 14], "span2": [182, 192]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11824": {"label": 1, "data": {"text": "In preclinical studies, the mammalian target of rapamycin (mTOR) in the medial prefrontal cortex and the eukaryotic elongation factor (eEF2) in the hippocampus have been proposed as critical mediators of ketamine's rapid antidepressant actions.", "entity1": "mammalian target of rapamycin", "entity2": "ketamine", "span1": [28, 57], "span2": [204, 212]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13509": {"label": 6, "data": {"text": "Allosteric interaction of the neuromuscular blockers vecuronium and pancuronium with recombinant human muscarinic M2 receptors.", "entity1": "human muscarinic M2 receptors", "entity2": "pancuronium", "span1": [97, 126], "span2": [68, 79]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1]},
	"11311": {"label": 1, "data": {"text": "Synthesis and in vitro pharmacology at AMPA and kainate preferring glutamate receptors of 4-heteroarylmethylidene glutamate analogues.", "entity1": "glutamate receptors", "entity2": "AMPA", "span1": [67, 86], "span2": [39, 43]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8547": {"label": 3, "data": {"text": "Herein we report novel pyrrole- and benzene-based hydroxamates (8, 10) and 2'-aminoanilides (9, 11) bearing the tert-butylcarbamate group at the CAP moiety as histone deacetylase (HDAC) inhibitors.", "entity1": "HDAC", "entity2": "tert-butylcarbamate", "span1": [180, 184], "span2": [112, 131]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2305": {"label": 1, "data": {"text": "These results indicate that sulindac metabolites modulate ERK1/2 and PKG pathways independently in colon cancer cells and suggest that the full apoptotic effect of sulindac is mediated by more than one pathway.", "entity1": "PKG", "entity2": "sulindac", "span1": [69, 72], "span2": [28, 36]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14636": {"label": 8, "data": {"text": "Gemcitabine (dFdC, 2',2'-difluorodeoxycytidine) is metabolized by cytidine deaminase (CDA) and deoxycytidine kinase (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.", "entity1": "cytidine deaminase", "entity2": "dFdC", "span1": [66, 84], "span2": [13, 17]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12330": {"label": 0, "data": {"text": "Using site-directed mutagenesis, we identified three serines (Ser833, Ser836, and Ser840) within the membrane proximal region of the GluK5 C-terminal domain that, in combination, are required for mGlu1-mediated potentiation of KARs.", "entity1": "GluK5", "entity2": "serines", "span1": [133, 138], "span2": [53, 60]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10330": {"label": 4, "data": {"text": "The immune response modifiers, imiquimod and resiquimod, are TLR7 agonists that induce type I interferon in numerous species, including humans.", "entity1": "TLR7", "entity2": "imiquimod", "span1": [61, 65], "span2": [31, 40]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2747": {"label": 3, "data": {"text": "PURPOSE: Dasatinib (BMS-354825), a potent oral multi-targeted kinase inhibitor against SRC and BCR-ABL, has recently been approved for the treatment of chronic myelogenous leukaemia (CML) in imatinib-acquired resistance and intolerance.", "entity1": "kinase", "entity2": "BMS-354825", "span1": [62, 68], "span2": [20, 30]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10776": {"label": 3, "data": {"text": "Imatinib mesylate is a tyrosine kinase inhibitor of the ABL, platelet-derived growth factor receptor (PDGFR), and c-kit kinases.", "entity1": "c-kit", "entity2": "Imatinib mesylate", "span1": [114, 119], "span2": [0, 17]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7461": {"label": 8, "data": {"text": "Together, these results suggest that an increased cytosolic availability of glycine in VIAAT-containing terminals was crucial for the emergence of glycinergic transmission in vertebrates.", "entity1": "VIAAT", "entity2": "glycine", "span1": [87, 92], "span2": [76, 83]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13185": {"label": 1, "data": {"text": "Synthesis, radiosynthesis, and biological evaluation of carbon-11 labeled 2beta-carbomethoxy-3beta-(3'-((Z)-2-haloethenyl)phenyl)nortropanes: candidate radioligands for in vivo imaging of the serotonin transporter with positron emission tomography.", "entity1": "serotonin transporter", "entity2": "carbon-11 labeled 2beta-carbomethoxy-3beta-(3'-((Z)-2-haloethenyl)phenyl)nortropanes", "span1": [192, 213], "span2": [56, 140]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"3731": {"label": 3, "data": {"text": "The present results indicated that N-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways.", "entity1": "ERK", "entity2": "BPs", "span1": [232, 235], "span2": [37, 40]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2828": {"label": 3, "data": {"text": "Pharmacological treatment has been studied and it could be demonstrated, that some mutant currents may be insufficiently suppressed by drugs targeted to block the specific current such as, e.g., sotalol or ibutilide in patients with a mutation in the IKr-coding gene KCNH2 (HERG).", "entity1": "HERG", "entity2": "sotalol", "span1": [274, 278], "span2": [195, 202]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10247": {"label": 8, "data": {"text": "Substrate specificity using lysates of oxidase-transfected HEK-293 cells revealed that the newly identified oxidase strongly favoured spermine over N (1)-acetylspermine and that it failed to act on N (1)-acetylspermidine, spermidine or the preferred PAO substrate, N (1), N (12)-diacetylspermine.", "entity1": "oxidase", "entity2": "N (1)-acetylspermine", "span1": [108, 115], "span2": [148, 168]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"15969": {"label": 1, "data": {"text": "We recently showed that the first domain of human CCS (hCCSD1) is responsible for copper transfer to its protein partner, human SOD1 (hSOD1).", "entity1": "hSOD1", "entity2": "copper", "span1": [134, 139], "span2": [82, 88]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15095": {"label": 3, "data": {"text": "Ceftazidime-avibactam appears to be well tolerated in healthy subjects and hospitalized patients, with few serious drug-related treatment-emergent adverse events reported to date.In conclusion, avibactam serves to broaden the spectrum of ceftazidime versus \u00df-lactamase-producing Gram-negative bacilli.", "entity1": "\u00df-lactamase", "entity2": "ceftazidime", "span1": [257, 268], "span2": [238, 249]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"7468": {"label": 1, "data": {"text": "Additionally, Na+ and Cl- ions coactivate GluR6 receptors by establishing a dipole, accounting for their common effect on KARs.", "entity1": "KARs", "entity2": "Na+", "span1": [122, 126], "span2": [14, 17]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15556": {"label": 1, "data": {"text": "A low molecular weight polyethyleneimine modified with deoxycholic acid (PEI1.8-DA)-based delivery strategy was suggested for the cardiac application of SHP-1 siRNA to overcome the poor gene delivery efficiency to myocardium due to the highly charged structures of the compact cardiac muscles.", "entity1": "SHP-1", "entity2": "deoxycholic acid", "span1": [153, 158], "span2": [55, 71]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3033": {"label": 8, "data": {"text": "Both risperidone and 9-hydroxyrisperidone are substrates of P-glycoprotein (P-gp), a transport protein involved in drug absorption, distribution, and elimination.", "entity1": "P-glycoprotein", "entity2": "9-hydroxyrisperidone", "span1": [60, 74], "span2": [21, 41]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, 8, -1, -1, -1, -1]},
	"14163": {"label": 5, "data": {"text": "The agonist activity was antagonized by the selective kappa-opioid blocker nor-binaltorphimine (nor-BNI).", "entity1": "kappa-opioid", "entity2": "nor-BNI", "span1": [54, 66], "span2": [96, 103]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7010": {"label": 3, "data": {"text": "Significant advances in the treatment of clear-cell RCC have been derived from agents that target these pathways, including the multiple-kinase inhibitors (MKIs) sorafenib, sunitinib, and AG013736, which target multiple VEGFRs as well as PDGFR-beta.", "entity1": "VEGFRs", "entity2": "AG013736", "span1": [220, 226], "span2": [188, 196]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9893": {"label": 1, "data": {"text": "UNLABELLED: Apparent muscarinic acetylcholine (mAch) receptor occupancy in mouse cerebral cortex, hippocampus, and striatum by scopolamine, an antagonist, and biperiden, a relatively selective M1 antagonist, was estimated with competitive binding studies using two different radioligands: 3H-N-methyl piperidyl benzilate (3H-NMPB) and 3H-quinuclidinyl benzilate (3H-QNB).", "entity1": "muscarinic acetylcholine (mAch) receptor", "entity2": "3H-N-methyl piperidyl benzilate", "span1": [21, 61], "span2": [289, 320]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8739": {"label": 1, "data": {"text": "In conclusion, this study expands the understanding of the substrate specificity of UGT2B10, highlighting its preference for tertiary amines with higher affinities and clearance values than those of UGT1A4 and UGT1A3.", "entity1": "UGT1A3", "entity2": "tertiary amines", "span1": [210, 216], "span2": [125, 140]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"9736": {"label": 1, "data": {"text": "In [(35)S]GTPgammaS binding protocols, yohimbine exerts antagonist actions at halpha(2A)-AR, h5-HT(1B), h5-HT(1D), and hD(2) sites, yet partial agonist actions at h5-HT(1A) sites.", "entity1": "halpha(2A)-AR", "entity2": "(35)S", "span1": [78, 91], "span2": [4, 9]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14859": {"label": 2, "data": {"text": "Using surface biotinylation, we observed that treatment of N-38 neurons with estradiol or with a membrane impermeant estradiol elevated plasma membrane ER\u03b1 protein levels, indicating that membrane signaling increased receptor insertion into the cell membrane.", "entity1": "ER\u03b1", "entity2": "estradiol", "span1": [152, 155], "span2": [117, 126]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9848": {"label": 9, "data": {"text": "Salicylates do not promote dissociation of (125)I-ET-1 ETB receptor complexes.", "entity1": "ET-1", "entity2": "Salicylates", "span1": [50, 54], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9686": {"label": 1, "data": {"text": "Ziprasidone is a novel antipsychotic agent which binds with high affinity to 5-HT1A receptors (Ki = 3.4 nM), in addition to 5-HT1D, 5-HT2, and D2 sites.", "entity1": "5-HT1D", "entity2": "Ziprasidone", "span1": [124, 130], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7506": {"label": 2, "data": {"text": "Additional pharmacological effects evoked by AICAR and phenformin on I(ouabain), with potential secondary effects on apical Na+ conductance, ENaC activity and monolayer resistance, have important consequences for their use as pharmacological activators of AMPK in cell systems where Na+K+ATPase is an important component.", "entity1": "AMPK", "entity2": "AICAR", "span1": [256, 260], "span2": [45, 50]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6257": {"label": 1, "data": {"text": "Among neuroleptics, the four most potent compounds at the human serotonin transporter were triflupromazine, fluperlapine, chlorpromazine, and ziprasidone (K(D) 24-39 nM); and at the norepinephrine transporter, chlorpromazine, zotepine, chlorprothixene, and promazine (K(D) 19-25 nM).", "entity1": "norepinephrine transporter", "entity2": "promazine", "span1": [182, 208], "span2": [257, 266]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"15159": {"label": 2, "data": {"text": "GnRH pulse frequency-dependent stimulation of FSH\u03b2 transcription is mediated via activation of PKA and CREB.", "entity1": "CREB", "entity2": "GnRH", "span1": [103, 107], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2463": {"label": 0, "data": {"text": "A premature stop codon (TGA) replaces the expected tryptophan codon at position seven of GnRH-II in sheep DNA.", "entity1": "GnRH-II", "entity2": "tryptophan", "span1": [89, 96], "span2": [51, 61]}, "weak_labels": [-1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"965": {"label": 9, "data": {"text": "Neither U50,488H nor etorphine caused down-regulation of the rat kappa-opioid receptor.", "entity1": "rat kappa-opioid receptor", "entity2": "U50,488H", "span1": [61, 86], "span2": [8, 16]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2908": {"label": 3, "data": {"text": "In view of its substantial COX-2 inhibition, recently defined cardiovascular warnings for use of COX-2 inhibitors should also be considered for acetaminophen.", "entity1": "COX-2", "entity2": "acetaminophen", "span1": [27, 32], "span2": [144, 157]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10568": {"label": 1, "data": {"text": "To verify the hypothesis that the non-conventional partial agonist (-)-CGP12177 binds at two beta(1)-adrenoceptor sites, human beta(1)-adrenoceptors, expressed in CHO cells, were labelled with (-)-[(3)H]-CGP12177.", "entity1": "beta(1)-adrenoceptor", "entity2": "(-)-CGP12177", "span1": [93, 113], "span2": [67, 79]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5722": {"label": 9, "data": {"text": "Indomethacin, used to inhibit cyclooxygenase, also inhibits AKR1C3 and displays selectivity over AKR1C1/AKR1C2.", "entity1": "AKR1C2", "entity2": "Indomethacin", "span1": [104, 110], "span2": [0, 12]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"994": {"label": 3, "data": {"text": "Given that FRD, present in all H. pylori strains, is immunogenic in H. pylori -infected patients and H. pylori growth in vitro can be inhibited by three anthelmintics (morantel, oxantel and thiabendazole), this enzyme could potentially be used both as a novel drug target as well as in the development of vaccines for H. pylori prevention and eradication.", "entity1": "FRD", "entity2": "morantel", "span1": [11, 14], "span2": [168, 176]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9466": {"label": 1, "data": {"text": "The DP, IP and TP receptors showed high ligand binding specificity and only bound their own putative ligands with high affinity such as PGD2, BW245C and BW868C for DP, cicaprost, iloprost and isocabacyclin for IP, and S-145, I-BOP and GR 32191 for TP.", "entity1": "DP", "entity2": "PGD2", "span1": [164, 166], "span2": [136, 140]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7029": {"label": 1, "data": {"text": "Further, cholesterol metabolites, predominantly the oxysterols, the natural ligands for liver X receptor (LXR), induced these genes via upregulation of sterol regulatory element binding protein-1c (SREBP-1c) that bound to the regulatory regions of these genes.", "entity1": "LXR", "entity2": "cholesterol", "span1": [106, 109], "span2": [9, 20]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14456": {"label": 3, "data": {"text": "We found that Ag NPs were highly cytotoxic to hepatocytes (LC(50) lactate dehydrogenase: 2.5 \u03bcg/cm(2)) and affected hepatocyte homeostasis by reducing albumin release.", "entity1": "albumin", "entity2": "Ag", "span1": [151, 158], "span2": [14, 16]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3988": {"label": 3, "data": {"text": "In addition, BGG-mediated inhibition of AR prevented LPS-induced activation of JNK and p38 and lowered ROS levels, which could inhibit LPS-induced apoptosis.", "entity1": "p38", "entity2": "BGG", "span1": [87, 90], "span2": [13, 16]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10966": {"label": 5, "data": {"text": "After that, a wide range of concentrations of drugs, concomitantly with ATR (0.1 microM), was studied in the presence of haloperidol (HAL; 0.01 microM), a dopamine D2 antagonist.", "entity1": "dopamine D2", "entity2": "HAL", "span1": [155, 166], "span2": [134, 137]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12704": {"label": 1, "data": {"text": "These two alleles were shown previously to be associated with ivermectin susceptibility (HG1A) and resistance (HG1E), respectively.", "entity1": "HG1A", "entity2": "ivermectin", "span1": [89, 93], "span2": [62, 72]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8495": {"label": 3, "data": {"text": "AlCl3 markedly reduced AA performance and activities of cytochrome c oxidase (COX) and acetylcholinesterase (AChE) in all regions.", "entity1": "acetylcholinesterase", "entity2": "AlCl3", "span1": [87, 107], "span2": [0, 5]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11546": {"label": 8, "data": {"text": "However the regulatory mechanism of histamine synthesis by HDC remains to be elucidated.", "entity1": "HDC", "entity2": "histamine", "span1": [59, 62], "span2": [36, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8091": {"label": 0, "data": {"text": "We aim to \"tilt\" the stability of the H1 loop structure from a noncanonical conformation to a (humanized) type 1 canonical conformation by studying the effect of selected mutations to the amino acid sequence of the H1, H2, and proximal residues.", "entity1": "H1", "entity2": "amino acid", "span1": [215, 217], "span2": [188, 198]}, "weak_labels": [0, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15350": {"label": 8, "data": {"text": "Coumarin 7-hydroxylation, catalyzed by P450 2A13, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.", "entity1": "P450 2A13", "entity2": "Coumarin", "span1": [39, 48], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"10890": {"label": 1, "data": {"text": "To understand this interaction, we determined the crystal structure of PDXK in complex with (R)-roscovitine, N6-methyl-(R)-roscovitine, and O6-(R)-roscovitine, the two latter derivatives being designed to bind to PDXK but not to CDKs.", "entity1": "PDXK", "entity2": "O6-(R)-roscovitine", "span1": [213, 217], "span2": [140, 158]}, "weak_labels": [-1, -1, -1, 1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7138": {"label": 1, "data": {"text": "All PDE5 constructs had similar affinities for 3-isobutyl-1-methylxanthine, sildenafil, tadalafil, and UK-122764, but mutants containing a complete GAF-B had 7- to 18-fold higher affinity for vardenafil-based compounds compared with those lacking a complete GAF-B.", "entity1": "GAF-B", "entity2": "UK-122764", "span1": [148, 153], "span2": [103, 112]}, "weak_labels": [-1, -1, 0, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14850": {"label": 2, "data": {"text": "Interestingly, Acrolein increased proteins' levels of amyloid precursor protein (APP), \u03b2-secretase (BACE-1) and the amyloid \u03b2-peptide transporter receptor for advanced glycation end products, and decreased A-disintegrin and metalloprotease (ADAM) 10 levels.", "entity1": "amyloid precursor protein", "entity2": "Acrolein", "span1": [54, 79], "span2": [15, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, 8, -1, 8, -1, -1]},
	"2142": {"label": 1, "data": {"text": "Effect of thiazolidinediones on equilibrative nucleoside transporter-1 in human aortic smooth muscle cells.", "entity1": "equilibrative nucleoside transporter-1", "entity2": "thiazolidinediones", "span1": [32, 70], "span2": [10, 28]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"2446": {"label": 9, "data": {"text": "Colonic cyclooxygenase-2 and interkeukin-1beta mRNA and spinal c-FOS mRNA expression were significantly down-regulated by ATB-429, but not by mesalamine.", "entity1": "c-FOS", "entity2": "mesalamine", "span1": [63, 68], "span2": [142, 152]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"8895": {"label": 4, "data": {"text": "The potent anabolic effects of the beta 2-adrenoceptor agonist clenbuterol on skeletal muscle have been reported to be independent of actions on beta-adrenoceptors.", "entity1": "beta 2-adrenoceptor", "entity2": "clenbuterol", "span1": [35, 54], "span2": [63, 74]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9367": {"label": 1, "data": {"text": "Binding of thalidomide to alpha1-acid glycoprotein may be involved in its inhibition of tumor necrosis factor alpha production.", "entity1": "alpha1-acid glycoprotein", "entity2": "thalidomide", "span1": [26, 50], "span2": [11, 22]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"11476": {"label": 0, "data": {"text": "Functional divergence of a unique C-terminal domain of leucylleucyl-tRNA synthetase to accommodate its splicing and aminoacylation roles.", "entity1": "leucyl-tRNA synthetase", "entity2": "leucyl", "span1": [61, 83], "span2": [55, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8182": {"label": 1, "data": {"text": "Although tamoxifen (TAM), a selective estrogen receptor modulator, has been widely used in the treatment of hormone-responsive breast cancer, its estrogen-like effect increases the risk of endometrial cancer.", "entity1": "estrogen receptor", "entity2": "tamoxifen", "span1": [38, 55], "span2": [9, 18]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11525": {"label": 8, "data": {"text": "Estrogens are biosynthesised from androgens by the CYP450 enzyme complex called aromatase.", "entity1": "CYP450", "entity2": "Estrogens", "span1": [51, 57], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11112": {"label": 1, "data": {"text": "Finally, a third nonadrenergic internal membrane site, labeled by [3H]IDX, was consistent with a subtype-I2 imidazol(in)e receptor site (rank order: cirazoline > IDX >> amiloride > moxonidine > clonidine).", "entity1": "subtype-I2 imidazol(in)e receptor", "entity2": "cirazoline", "span1": [97, 130], "span2": [149, 159]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5647": {"label": 2, "data": {"text": "Arsenic trioxide-induced hERG K(+) channel deficiency can be rescued by matrine and oxymatrine through up-regulating transcription factor Sp1 expression.", "entity1": "K(+) channel", "entity2": "matrine", "span1": [30, 42], "span2": [72, 79]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2611": {"label": 8, "data": {"text": "Possession of CYP2C9*2 or CYP2C9*3 variant alleles, which result in decreased enzyme activity, is associated with a significant decrease in the mean warfarin dose.", "entity1": "CYP2C9", "entity2": "warfarin", "span1": [14, 20], "span2": [149, 157]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7702": {"label": 2, "data": {"text": "atropine, AChE reactivator such as one of the recommended pyridinium oximes (pralidoxime, trimedoxime, obidoxime and HI-6) and diazepam are used for the treatment of OP poisoning in humans.", "entity1": "AChE", "entity2": "HI-6", "span1": [10, 14], "span2": [117, 121]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1175": {"label": 3, "data": {"text": "Patch-clamp analysis using inside-out recording configuration showed that mitiglinide inhibits the Kir6.2/SUR1 channel currents in a dose-dependent manner (IC50 value, 100 nM) but does not significantly inhibit either Kir6.2/SUR2A or Kir6.2/SUR2B channel currents even at high doses (more than 10 microM).", "entity1": "Kir6.2", "entity2": "mitiglinide", "span1": [99, 105], "span2": [74, 85]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3061": {"label": 3, "data": {"text": "Plerixafor (AMD3100, Genzyme Corporation) is a bicyclam molecule that antagonizes the binding of the chemokine stromal cell-derived factor-1 (SDF-1) to its cognate receptor CXCR4.", "entity1": "CXCR4", "entity2": "bicyclam", "span1": [173, 178], "span2": [47, 55]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15785": {"label": 8, "data": {"text": "A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the oxidosqualene cyclase(1) (OSC)-mediated cyclization of 2,3-oxidosqualen to lanosterol was prepared from Grundmann's ketone.", "entity1": "OSC", "entity2": "2,3-oxidosqualen", "span1": [123, 126], "span2": [152, 168]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13402": {"label": 1, "data": {"text": "It is currently not known how much this H(1) antagonism of clozapine contributes to the therapeutic or adverse side effects of clozapine.", "entity1": "H(1)", "entity2": "clozapine", "span1": [40, 44], "span2": [127, 136]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"15114": {"label": 2, "data": {"text": "These findings are the first to show that long-term exposure to Mn during a critical period of neurodevelopment causes motor coordination dysfunction with parallel increment in oxidative stress markers, p38(MAPK) phosphorylation and caspase activity in the striatum.", "entity1": "p38", "entity2": "Mn", "span1": [203, 206], "span2": [64, 66]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9231": {"label": 8, "data": {"text": "Alanine:glyoxylate aminotransferase (AGT) in the liver catalyzes most of the glyoxylate transamination in mammalian tissues (E. V. Rowsell, K. Snell, J.", "entity1": "Alanine:glyoxylate aminotransferase", "entity2": "glyoxylate", "span1": [0, 35], "span2": [77, 87]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, 9]},
	"3111": {"label": 3, "data": {"text": "In summary, ketoconazole had no clinically significant effect on the pharmacokinetics or safety profile of ambrisentan; therefore, no changes in ambrisentan dose should be necessary when the drug is administered concomitantly with known CYP3A4 inhibitors.", "entity1": "CYP3A4", "entity2": "ketoconazole", "span1": [237, 243], "span2": [12, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8260": {"label": 4, "data": {"text": "Commercially-available 5-HT2C agonists (CP 809101, Ro 60-0175, WAY 161503, mCPP, and 1-methylpsilocin), novel\u00a04-phenyl-2-N,N-dimethyl-aminotetralin (PAT)-type 5-HT2C agonists (with 5-HT2A/2B antagonist activity), and antagonists selective for 5-HT2A (M100907), 5-HT2C (SB-242084), and 5-HT2B/2C (SB-206553) receptors attenuated the DOI-elicited-HTR.", "entity1": "5-HT2C", "entity2": "mCPP", "span1": [23, 29], "span2": [75, 79]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9345": {"label": 3, "data": {"text": "Although DEC exerts local antioxidant activity with beneficial effects on lung tissue, this 5-LO inhibitor intensifies the blast overpressure caused hemodynamic insufficiency.", "entity1": "5-LO", "entity2": "DEC", "span1": [92, 96], "span2": [9, 12]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8936": {"label": 1, "data": {"text": "Both these MAPs were found to have two to three binding sites for estramustine phosphate which is compatible with the reported number of basic amino acid repeats of these MAPs, considered to be the ultimate tubulin binding domains.", "entity1": "MAPs", "entity2": "estramustine phosphate", "span1": [11, 15], "span2": [66, 88]}, "weak_labels": [0, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13130": {"label": 2, "data": {"text": "RESULT(S): The expression of endometrial ERalpha, PRAB, PRB, and SRC-1 was increased significantly after 1 week of mifepristone, but the increase was no longer seen after 10 weeks.", "entity1": "PRB", "entity2": "mifepristone", "span1": [56, 59], "span2": [115, 127]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3221": {"label": 3, "data": {"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1).", "entity1": "EC 4.2.1.1", "entity2": "syringic acid", "span1": [286, 296], "span2": [145, 158]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"3168": {"label": 1, "data": {"text": "A few compounds, 17alpha-methyltestosterone (17alpha-MT), vinclozolin and linuron, were studied using a real world scenario, i.e., assuming that their interaction with the AR was not known: A prescreening for agonism and true, competitive antagonism was used to select conditions such as the appropriate mode of action, and the working range excluding cytotoxicity for the final screening.", "entity1": "AR", "entity2": "linuron", "span1": [172, 174], "span2": [74, 81]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"15254": {"label": 1, "data": {"text": "Selective oxidation of \u03c9-tertiary amine self-assembled thiol monolayers to tertiary amine N-oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them.", "entity1": "lysozyme", "entity2": "\u03c9-tertiary amine", "span1": [152, 160], "span2": [23, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11503": {"label": 0, "data": {"text": "New data for cattle (Bos taurus) indicates a gene encoding GnRH-II decapeptide possessing arginine (codon: CGG) rather than tryptophan (TGG) at position three in the mature peptide.", "entity1": "GnRH-II", "entity2": "arginine", "span1": [59, 66], "span2": [90, 98]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12929": {"label": 8, "data": {"text": "Hydrogen sulfide (H(2)S), a regulatory gaseous molecule that is endogenously synthesized by cystathionine gamma-lyase (CSE) and/or cystathionine beta-synthase (CBS) from L-cysteine (L-Cys) metabolism, is a putative vasodilator, and its role in nitric oxide (NO) production is unexplored.", "entity1": "cystathionine gamma-lyase", "entity2": "L-cysteine", "span1": [92, 117], "span2": [170, 180]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"6598": {"label": 4, "data": {"text": "However, 5-HT(1A) agonism may be important only for quetiapine-induced ACh release.", "entity1": "5-HT(1A)", "entity2": "quetiapine", "span1": [9, 17], "span2": [52, 62]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14803": {"label": 3, "data": {"text": "Trichostatin A inhibits transforming growth factor-\u03b2-induced reactive oxygen species accumulation and myofibroblast differentiation via enhanced NF-E2-related factor 2-antioxidant response element signaling.", "entity1": "transforming growth factor-\u03b2", "entity2": "Trichostatin A", "span1": [24, 52], "span2": [0, 14]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3275": {"label": 3, "data": {"text": "Using a unique biosensor-based assay, trifluoperazine (TFP) was identified as an inhibitor that disrupts the S100A4/myosin-IIA interaction.", "entity1": "myosin-IIA", "entity2": "trifluoperazine", "span1": [116, 126], "span2": [38, 53]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3943": {"label": 3, "data": {"text": "Inhibition by phenformin of oxygen consumption via complex I respiration in isolated rat liver mitochondria was greater than that in heart mitochondria, whereas inhibitory effect of phenformin on complex I respiration was similar in inside-out structured submitochondrial particles prepared from rat livers and hearts.", "entity1": "complex I", "entity2": "phenformin", "span1": [51, 60], "span2": [14, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13677": {"label": 1, "data": {"text": "Two imidazoquinoline molecules, imiquimod and gardiquimod, markedly activated both porcine TLR7 and TLR8 whereas only human TLR7, but not TLR8, was activated by the ligands.", "entity1": "TLR8", "entity2": "imidazoquinoline", "span1": [100, 104], "span2": [4, 20]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3884": {"label": 3, "data": {"text": "3D-QSAR-assisted drug design: identification of a potent quinazoline-based Aurora kinase inhibitor.", "entity1": "Aurora kinase", "entity2": "quinazoline", "span1": [75, 88], "span2": [57, 68]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7353": {"label": 1, "data": {"text": "Immature (reticulated) platelets may modulate the antiplatelet effects of aspirin through uninhibited cyclooxygenase (COX)-1 and COX-2.", "entity1": "(COX)-1", "entity2": "aspirin", "span1": [117, 124], "span2": [74, 81]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7482": {"label": 1, "data": {"text": "Phenserine deserves attention for an additional quality of action: in addition to inhibiting AChE, it modulates the amount of beta-amyloid precursor protein (APP) in neuronal cell culture by reducing APP translation.", "entity1": "APP", "entity2": "Phenserine", "span1": [158, 161], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5325": {"label": 1, "data": {"text": "Pasireotide (Signifor(\u00ae)) is a new subcutaneous somatostatin analogue that acts via somatostatin receptors to inhibit the secretion of corticotropin from the pituitary adenoma in patients with Cushing's disease.", "entity1": "somatostatin receptors", "entity2": "Pasireotide", "span1": [84, 106], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15422": {"label": 1, "data": {"text": "This study evaluates the production of inflammatory biomarkers (IL-1\u03b2, IL-8, IL-10, TNF\u03b1) and the influence of gene expression transporters and enzymes related to cholesterol absorption and metabolism (NPC1L1, ABCG5/8, HMGCoA, ACAT) produced by 7-ketosterols (stigmasterol/cholesterol) in Caco-2 cells.", "entity1": "ACAT", "entity2": "cholesterol", "span1": [227, 231], "span2": [273, 284]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 8, -1, -1]},
	"11229": {"label": 1, "data": {"text": "The effects of mitiglinide (KAD-1229), a new anti-diabetic drug, on ATP-sensitive K+ channels and insulin secretion: comparison with the sulfonylureas and nateglinide.", "entity1": "ATP-sensitive K+ channels", "entity2": "mitiglinide", "span1": [68, 93], "span2": [15, 26]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9158": {"label": 3, "data": {"text": "Gossypol and its isomers were non-competitive inhibitors of human and hamster LDH-X with respect to the coenzyme NADH, competitive inhibitors of human LDH-X and noncompetitive-competitive inhibitors of hamster LDH-X with respect to the substrate alpha-ketobutyrate.", "entity1": "human LDH-X", "entity2": "NADH", "span1": [145, 156], "span2": [113, 117]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"15034": {"label": 8, "data": {"text": "All the compounds were evaluated for their anti-tumor activity against MCF-7, A549 and B16-F10 tumor cell lines as well as cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) inhibitory activity of murine macrophage RAW 264.7 cell line.", "entity1": "COX-2", "entity2": "prostaglandin E2", "span1": [141, 146], "span2": [156, 172]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5975": {"label": 3, "data": {"text": "Phenol oxidase inhibitors such as phenylthiourea, potassium cyanide, and sodium azide inhibited the reaction drastically, suggesting the participation of the active site copper of the enzyme in the catalysis.", "entity1": "Phenol oxidase", "entity2": "sodium azide", "span1": [0, 14], "span2": [73, 85]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"9307": {"label": 3, "data": {"text": "The present study utilized blood from normal volunteers and 125I-fibrinogen in a dilute whole blood clot assay to determine the relative concentrations of lysine analogues required for inhibition of clot lysis induced by exogenous t-PA.", "entity1": "t-PA", "entity2": "lysine", "span1": [231, 235], "span2": [155, 161]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11590": {"label": 8, "data": {"text": "Differences in magnitude of Na(+)-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in ASCT2 protein expression, this being more abundant in WKY PTE cells.", "entity1": "ASCT2", "entity2": "l-alanine", "span1": [69, 74], "span2": [44, 53]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10599": {"label": 1, "data": {"text": "Both the abundance of transferrin receptors and upregulation of ribonucleotide reductase render tumors susceptible to gallium-induced cytotoxicity.", "entity1": "transferrin receptors", "entity2": "gallium", "span1": [22, 43], "span2": [118, 125]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, 2, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5810": {"label": 1, "data": {"text": "The reducing activity of alpha N-acetyl beta-endorphin-(1-31) upon morphine- and beta-endorphin-induced analgesia was not exhibited in mice undergoing treatment with pertussis toxin or N-ethylmaleimide, agents known to impair the function of Gi/Go transducer proteins.", "entity1": "Go", "entity2": "N-ethylmaleimide", "span1": [245, 247], "span2": [185, 201]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"10615": {"label": 1, "data": {"text": "Furthermore, GABA receptors of horizontal cells were modulated by extracellular application of diazepam, zolpidem, methyl 6,7-dimethoxy-4-ethyl-beta-carboxylate, pentobarbital, and alphaxalone, thus showing typical pharmacological properties of CNS GABAA receptors.", "entity1": "GABA receptors", "entity2": "diazepam", "span1": [13, 27], "span2": [95, 103]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5089": {"label": 1, "data": {"text": "Aldosterone-induced ENaC and basal Na(+)/K(+)-ATPase trafficking via protein kinase D1-phosphatidylinositol 4-kinaseIII\u03b2 trans Golgi signalling in M1 cortical collecting duct cells.", "entity1": "protein kinase D1", "entity2": "Aldosterone", "span1": [69, 86], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2402": {"label": 9, "data": {"text": "When HUVECs were stimulated by thrombin in the presence of 100 microM L-arginine, NOS activity and NO release were similar in untreated and Nor-NOHA-treated cells.", "entity1": "NOS", "entity2": "Nor-NOHA", "span1": [82, 85], "span2": [140, 148]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"701": {"label": 5, "data": {"text": "The putative alpha 1L-adrenoceptor antagonist JTH-601, but not the alpha 1B-adrenoceptor antagonist chloroethylclonidine (10 microM) antagonized noradrenaline-induced contractions of SMA.", "entity1": "alpha 1L-adrenoceptor", "entity2": "JTH-601", "span1": [13, 34], "span2": [46, 53]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7750": {"label": 3, "data": {"text": "Further, we used this model to test the efficacy of GDC-0941, a PI3K inhibitor, in clinical development, and showed that the tumors respond to PI3K inhibition.", "entity1": "PI3K", "entity2": "GDC-0941", "span1": [64, 68], "span2": [52, 60]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2351": {"label": 4, "data": {"text": "Effect of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide (ramelteon, TAK-375), a selective MT1/MT2 receptor agonist, on motor coordination was studied using rota-rod performance in mice.", "entity1": "MT1/MT2 receptor", "entity2": "TAK-375", "span1": [120, 136], "span2": [98, 105]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10762": {"label": 2, "data": {"text": "Western blot analysis of cells incubated with imatinib demonstrated activation of EGFR and downstream signaling that was reduced by inhibition of mitogen-activated protein/extracellular signal-regulated kinase kinase 1 (MEK1) and EGFR, but not Her2/ErbB2.", "entity1": "EGFR", "entity2": "imatinib", "span1": [82, 86], "span2": [46, 54]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3231": {"label": 3, "data": {"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1).", "entity1": "carbonic anhydrase", "entity2": "phenol", "span1": [262, 280], "span2": [31, 37]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"8513": {"label": 3, "data": {"text": "To overcome this limitation, we de novo synthesized a conjugate that covalently combines a Gd-based MRI contrast agent, encaged with a chelating agent (DOTA), with pantoprazole, which is a widely used proton pump inhibitor that binds to proton pumps in the stomach and colon.", "entity1": "proton pump", "entity2": "Gd", "span1": [201, 212], "span2": [91, 93]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10215": {"label": 2, "data": {"text": "In the present study, we evaluated whether therapeutic doses of metformin increase AMPK activity in vivo in subjects with type 2 diabetes.", "entity1": "AMPK", "entity2": "metformin", "span1": [83, 87], "span2": [64, 73]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5955": {"label": 3, "data": {"text": "Levels of homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and dihydroxyphenylglycol (DHPG) in plasma and the striatium were measured after inhibition of monoamine oxidase type A (MAO-A) by clorgyline (4 mg/kg i.p.", "entity1": "monoamine oxidase type A", "entity2": "clorgyline", "span1": [165, 189], "span2": [201, 211]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14998": {"label": 1, "data": {"text": "Both fatty acids, but DHA to a lesser extent compared with EPA, selectively and dose-dependently reduced the percentage of cytokine-expressing Th cells in a peroxisome proliferator-activated receptor (PPAR)\u03b3-dependent fashion, whereas the expression of the cell surface marker CD69 was unaltered on activated T cells.", "entity1": "peroxisome proliferator-activated receptor (PPAR)\u03b3", "entity2": "EPA", "span1": [157, 207], "span2": [59, 62]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14608": {"label": 8, "data": {"text": "Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.", "entity1": "CDA", "entity2": "dFdC", "span1": [34, 37], "span2": [230, 234]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"2325": {"label": 3, "data": {"text": "A pronounced NET knockout-induced shortening of the immobility time in the TST (by ca 50%) compared to WT mice was not reduced any further by NET-inhibiting ADs such as reboxetine, desipramine, and imipramine.", "entity1": "NET", "entity2": "desipramine", "span1": [142, 145], "span2": [181, 192]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"14823": {"label": 3, "data": {"text": "Dabigatran has an advantage over the indirect thrombin inhibitors, unfractionated heparin and low-molecular-weight heparin, in that it inhibits free and fibrin-bound thrombin.", "entity1": "thrombin", "entity2": "Dabigatran", "span1": [166, 174], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8358": {"label": 3, "data": {"text": "Amino acid derived quinazolines as Rock/PKA inhibitors.", "entity1": "PKA", "entity2": "Amino acid", "span1": [40, 43], "span2": [0, 10]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11253": {"label": 1, "data": {"text": "The 4',7,8-trichloro analogue (38) of mazindol was the most potent and selective ligand for HEK-hDAT cells (DAT K(i) = 1.1 nM; SERT/DAT = 1283 and NET/DAT = 38).", "entity1": "DAT", "entity2": "mazindol", "span1": [132, 135], "span2": [38, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"651": {"label": 3, "data": {"text": "Both BB-94 and captopril also prevented substrate degradation by gelatinase A and B released in conditioned medium by cultured cells.", "entity1": "gelatinase A and B", "entity2": "BB-94", "span1": [65, 83], "span2": [5, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"12975": {"label": 6, "data": {"text": "Diacylglycerol (DAG) acts as an allosteric activator of protein kinase C (PKC) and is converted to phosphatidic acid by DAG kinase (DGK).", "entity1": "protein kinase C", "entity2": "Diacylglycerol", "span1": [56, 72], "span2": [0, 14]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, 8, -1]},
	"14621": {"label": 8, "data": {"text": "Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.", "entity1": "Pro122Ser", "entity2": "2',2'-difluorodeoxyuridine", "span1": [96, 105], "span2": [255, 281]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"131": {"label": 3, "data": {"text": "Felodipine and the p-chloro analogue inhibited the basal (Ca2+/calmodulin-independent) activity of cAMP phosphodiesterase as well as the calmodulin-stimulated activity.", "entity1": "cAMP phosphodiesterase", "entity2": "Felodipine", "span1": [99, 121], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4952": {"label": 1, "data": {"text": "In this study, we have demonstrated that fisetin prevents diet-induced obesity through regulation of the signaling of mammalian target of rapamycin complex 1 (mTORC1), a central mediator of cellular growth, cellular proliferation and lipid biosynthesis.", "entity1": "mTORC1", "entity2": "fisetin", "span1": [159, 165], "span2": [41, 48]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1892": {"label": 1, "data": {"text": "I3A was unable to cause the same extent of association of the C1b domain of PKC-delta with lipids, compared with PMA or the physiological regulator diacylglycerol, and was able to partially block the association induced by these agents, measured by surface plasmon resonance.", "entity1": "PKC-delta", "entity2": "diacylglycerol", "span1": [76, 85], "span2": [148, 162]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5293": {"label": 3, "data": {"text": "Vandetanib (Caprelsa(\u00ae), AstraZeneca) is a once-daily oral tyrosine kinase inhibitor that selectively inhibits signalling mediated by growth-factor receptor tyrosine kinase RET (constitutively activated in roughly 60\u00a0% of all MTCs), vascular endothelial growth-factor receptors 2 and 3, and epidermal growth-factor receptors.", "entity1": "tyrosine kinase", "entity2": "Caprelsa", "span1": [59, 74], "span2": [12, 20]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15038": {"label": 1, "data": {"text": "It had higher levels of oleocanthal (p-HPEA-EDA), a nutraceutical compound exerting actions against COX1 and COX2 (cycloxygenases).", "entity1": "COX2", "entity2": "oleocanthal", "span1": [109, 113], "span2": [24, 35]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6686": {"label": 2, "data": {"text": "TRPM8 (CMR1) is a Ca(2+)-permeable channel, which can be activated by low temperatures, menthol, eucalyptol and icilin.", "entity1": "CMR1", "entity2": "eucalyptol", "span1": [7, 11], "span2": [97, 107]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9036": {"label": 3, "data": {"text": "Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid.", "entity1": "5-lipoxygenase", "entity2": "sulfasalazine", "span1": [14, 28], "span2": [92, 105]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10062": {"label": 2, "data": {"text": "Like conventional ACE inhibitors, omapatrilat causes extracellular volume reduction and vasodilatation; moreover, it increases levels of atrial and brain natriuretic peptides and bradykinin.", "entity1": "atrial and brain natriuretic peptides", "entity2": "omapatrilat", "span1": [137, 174], "span2": [34, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"16074": {"label": 3, "data": {"text": "Ibrutinib (Imbruvica(R)) is a first-in-class, potent, orally administered, covalent inhibitor of Bruton's tyrosine kinase (BTK) that inhibits B-cell antigen receptor signalling downstream of BTK.", "entity1": "Bruton's tyrosine kinase", "entity2": "Imbruvica(R)", "span1": [97, 121], "span2": [11, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12763": {"label": 1, "data": {"text": "This study compared the sedative profiles of the second-generation antihistamines, fexofenadine and cetirizine, using 3 different criteria: subjective sleepiness evaluated by the Stanford Sleepiness Scale, objective psychomotor tests (simple and choice reaction time tests and visual discrimination tests at 4 different exposure durations), and measurement of histamine H1-receptor occupancy (H1RO) in the brain.", "entity1": "histamine H1-receptor", "entity2": "fexofenadine", "span1": [360, 381], "span2": [83, 95]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15310": {"label": 4, "data": {"text": "for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30\u200a\u03bcg/100\u200ag BW, oral) and were found to improve in the Bzf co-treated condition.", "entity1": "peroxisome proliferator-activated receptor alpha", "entity2": "bezafibrate", "span1": [28, 76], "span2": [85, 96]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13165": {"label": 1, "data": {"text": "Progestin induction of the cyclin D1 gene, which lacks a progesterone response element, was dependent on PR activation of the Src/MAPK pathway, whereas induction of the Sgk (serum and glucocorticoid regulated kinase) gene that contains a functional progesterone response element was unaffected by mutations that interfere with PR activation of Src.", "entity1": "cyclin D1", "entity2": "Progestin", "span1": [27, 36], "span2": [0, 9]}, "weak_labels": [-1, -1, 0, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11727": {"label": 8, "data": {"text": "The mitochondrial respiratory chain complex IV (cytochrome c oxidase) is a multi-subunit enzyme that transfers electrons from cytochrome c to molecular oxygen, yielding water.", "entity1": "mitochondrial respiratory chain complex IV", "entity2": "oxygen", "span1": [4, 46], "span2": [152, 158]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7330": {"label": 8, "data": {"text": "Na+-Dependent transmembrane transport of small neutral amino acids, such as glutamine and alanine, is mediated, among others, by the neutral amino acid transporters of the solute carrier 1 [SLC1, alanine serine cysteine transporter 1 (ASCT1), and ASCT2] and SLC38 families [sodium-coupled neutral amino acid transporter 1 (SNAT1), SNAT2, and SNAT4].", "entity1": "solute carrier 1", "entity2": "glutamine", "span1": [172, 188], "span2": [76, 85]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"319": {"label": 0, "data": {"text": "The refolding kinetics of guanidine-denatured disulfide-intact bovine pancreatic ribonuclease A (RNase A) and its proline-42-to-alanine mutant (Pro42Ala) have been studied by monitoring tyrosine burial and 2'-cytidine monophosphate (2'CMP) inhibitor binding.", "entity1": "RNase A", "entity2": "proline", "span1": [97, 104], "span2": [114, 121]}, "weak_labels": [-1, -1, 0, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10889": {"label": 1, "data": {"text": "To understand this interaction, we determined the crystal structure of PDXK in complex with (R)-roscovitine, N6-methyl-(R)-roscovitine, and O6-(R)-roscovitine, the two latter derivatives being designed to bind to PDXK but not to CDKs.", "entity1": "PDXK", "entity2": "O6-(R)-roscovitine", "span1": [71, 75], "span2": [140, 158]}, "weak_labels": [-1, -1, -1, 1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"865": {"label": 3, "data": {"text": "Depletion of putrescine, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "entity1": "ornithine decarboxylase", "entity2": "DFMO", "span1": [118, 141], "span2": [87, 91]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5410": {"label": 2, "data": {"text": "Type I deiodinase, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, while TDCPP induced CYP3A37 and CYP2H1.", "entity1": "CYP3A37", "entity2": "TDCPP", "span1": [151, 158], "span2": [137, 142]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11013": {"label": 9, "data": {"text": "We compared the effects of Captopril (an ACE inhibitor with -SH group), enalapril (an ACE-inhibitor without -SH group), N-acetylcysteine (only -SH group not ACE inhibitor) on endothelial dysfunction injured by methionine-induced hyperhomocysteinemia (HHcy) in rats.", "entity1": "ACE", "entity2": "N-acetylcysteine", "span1": [157, 160], "span2": [120, 136]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1629": {"label": 1, "data": {"text": "AIM: To study the changes in the expression and phosphorylation of cAMP response element binding protein (CREB) in the rat nucleus accumbens after chronic ethanol intake and its withdrawal.", "entity1": "CREB", "entity2": "ethanol", "span1": [106, 110], "span2": [155, 162]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6966": {"label": 1, "data": {"text": "As CRABPI was elevated far more than any other genes, we observed that the retinoids, all-trans retinoic acid and 9-cis retinoic acid, that bind CRABPI, promoted nitroblue tetrazolium-associated functional cell differentiation in p75NTR PC-3 cells, but not in neo control PC-3 cells.", "entity1": "CRABPI", "entity2": "9-cis retinoic acid", "span1": [145, 151], "span2": [114, 133]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1765": {"label": 1, "data": {"text": "beta(1)-adrenoceptor overexpression enhanced the inotropic potency of isoprenaline by 11.7-fold (pD(2) 8.76+/-0.14) and CGP 12177A by 5.9-fold (7.11+/-0.10), respectively.", "entity1": "beta(1)-adrenoceptor", "entity2": "isoprenaline", "span1": [0, 20], "span2": [70, 82]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9246": {"label": 2, "data": {"text": "Cells propagated in medium containing N5-methyltetrahydrofolate and homocysteine showed a substantial increase in MS activity which paralleled the increase in the intracellular concentration of Me-Cbl and the Cbl bound to the enzyme.", "entity1": "MS", "entity2": "N5-methyltetrahydrofolate", "span1": [114, 116], "span2": [38, 63]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14925": {"label": 1, "data": {"text": "However, other steroids, including \u0394(5)-androstenediol, 5\u03b1-androstanediol and 27-hydroxycholesterol, which have a saturated A ring containing a 3\u03b2-hydroxyl and a C19 methyl group, also mediate physiological responses through binding to estrogen receptor-\u03b1 (ER\u03b1) and ER\u03b2.", "entity1": "ER\u03b1", "entity2": "3\u03b2-hydroxyl", "span1": [257, 260], "span2": [144, 155]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6414": {"label": 2, "data": {"text": "Peroxisome proliferator-activated receptor alpha (PPARalpha) activators, bezafibrate and Wy-14,643, increase uncoupling protein-3 mRNA levels without modifying the mitochondrial membrane potential in primary culture of rat preadipocytes.", "entity1": "Peroxisome proliferator-activated receptor alpha", "entity2": "Wy-14,643", "span1": [0, 48], "span2": [89, 98]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10828": {"label": 9, "data": {"text": "The reported mechanism of imatinib resistance in GISTs involves missense mutation in the kinase domain of KIT, including Thr670Ile, Tyr823Asp, and Val654Ala.", "entity1": "KIT,", "entity2": "imatinib", "span1": [106, 110], "span2": [26, 34]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5183": {"label": 1, "data": {"text": "Dioscin-induced autophagy mitigates cell apoptosis through modulation of PI3K/Akt and ERK and JNK signaling pathways in human lung cancer cell lines.", "entity1": "JNK", "entity2": "Dioscin", "span1": [94, 97], "span2": [0, 7]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2388": {"label": 3, "data": {"text": "Sorafenib inhibited the kinase activity of both C-RAF and B-RAF (wild type and V600E mutant).", "entity1": "V600E", "entity2": "Sorafenib", "span1": [79, 84], "span2": [0, 9]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3600": {"label": 1, "data": {"text": "We found distinct differences in the action of ifenprodil at GluN1/GluN2B in comparison with previous studies on the effect of zinc on GluN1/GluN2A gating, which may arise due to their unique binding sites.", "entity1": "GluN1", "entity2": "ifenprodil", "span1": [61, 66], "span2": [47, 57]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1741": {"label": 8, "data": {"text": "CPT I (carnitine palmitoyltransferase I) catalyses the conversion of palmitoyl-CoA into palmitoylcarnitine in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria.", "entity1": "CPT I", "entity2": "palmitoylcarnitine", "span1": [0, 5], "span2": [88, 106]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 8, -1]},
	"6538": {"label": 1, "data": {"text": "Regulation of norepinephrine transporter abundance by catecholamines and desipramine in vivo.", "entity1": "norepinephrine transporter", "entity2": "catecholamines", "span1": [14, 40], "span2": [54, 68]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"11846": {"label": 1, "data": {"text": "A multivariable model adjusted for age, sex, population group, immigrant status, BMI, season of vitamin D measurement, LDL and HDL cholesterol, triglycerides, estimated glomerular filtration rate, history of hypertension or cardiovascular disease, Charlson comorbidity index, smoking, and socioeconomic status revealed an inverse association between 25-OHD and the risk of progression to IFG and diabetes.", "entity1": "HDL", "entity2": "25-OHD", "span1": [127, 130], "span2": [350, 356]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15085": {"label": 1, "data": {"text": "Potential future roles for ceftazidime-avibactam include the treatment of suspected or documented infections caused by resistant Gram-negative-bacilli producing extended-spectrum \u00df-lactamase (ESBL), Klebsiella pneumoniae carbapenemases (KPCs) and/or AmpC \u00df-lactamases.", "entity1": "Klebsiella pneumoniae carbapenemases", "entity2": "avibactam", "span1": [199, 235], "span2": [39, 48]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"1372": {"label": 1, "data": {"text": "The L0 linker has been reported to be required for glibenclamide binding, and DeltaNK(IR)6.2/SUR1 channels exhibit reduced labeling of K(IR) with (125)I-azidoglibenclamide, implying that the K(IR) N terminus and L0 of SUR1 are in proximity.", "entity1": "DeltaNK(IR)6.2", "entity2": "(125)I-azidoglibenclamide", "span1": [78, 92], "span2": [146, 171]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12602": {"label": 0, "data": {"text": "The predicted structure of PHBP showed three epidermal growth factor (EGF) domains, a kringle domain and a serine protease domain, from its N-terminus, although HGFA has a fibronectin type II domain, an EGF domain, a fibronectin type I domain, an EGF domain, a kringle domain, and a serine protease domain, from its N-terminus.", "entity1": "fibronectin type I domain", "entity2": "N", "span1": [217, 242], "span2": [316, 317]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8888": {"label": 3, "data": {"text": "By \"working upwards\" from mTOR, we observed that TCDD inhibited endogenous and IGF-I-induced AKT and ERK activation by interfering with tyrosine phosphorylation of insulin receptor substrate 1.", "entity1": "IGF-I", "entity2": "TCDD", "span1": [79, 84], "span2": [49, 53]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"4615": {"label": 3, "data": {"text": "Discovery of novel 2-hydroxydiarylamide derivatives as TMPRSS4 inhibitors.", "entity1": "TMPRSS4", "entity2": "2-hydroxydiarylamide", "span1": [55, 62], "span2": [19, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14183": {"label": 1, "data": {"text": "Mass spectral analysis of CBDP-inhibited BChE digested with Glu-C showed an o-hydroxybenzyl adduct (+106amu) on lysine 499, a residue far from the active site, but not on His-438.", "entity1": "BChE", "entity2": "o-hydroxybenzyl", "span1": [41, 45], "span2": [76, 91]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"10660": {"label": 2, "data": {"text": "Treatment of both differentiating adipocytes and fully differentiated adipocytes with telmisartan caused a dose-dependent increase in mRNA levels for PPARgamma target genes such as aP2 and adiponectin.", "entity1": "aP2", "entity2": "telmisartan", "span1": [181, 184], "span2": [86, 97]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3140": {"label": 1, "data": {"text": "We report here that amitriptyline, an antidepressant drug, directly binds TrkA and TrkB and triggers their dimerization and activation.", "entity1": "TrkA", "entity2": "amitriptyline", "span1": [74, 78], "span2": [20, 33]}, "weak_labels": [-1, -1, -1, 1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13198": {"label": 1, "data": {"text": "In vivo, cromolyn inhibited tumor growth in mice bearing tumor with endogenous S100P (BxPC-3: control, mean = 1.6 x 10(9) photons/s, versus cromolyn, mean = 4.4 x 10(8) photons/s, difference = 1.2 x 10(9) photons/s; 95% CI = 6.2 x 10(8) to 1.6 x 10(9) photons/s; P<.001, n = 5; MPanc-96: control, mean = 1.1 x 10(10) photons/s, versus cromolyn, mean = 4.8 x 10(9) photons/s, difference = 6.2 x 10(9) photons/s; 95% CI = 1.9 x 10(9) to 1.0 x 10(10) photons/s; P = .009, n = 5) and increased the effectiveness of gemcitabine (BxPC-3: gemcitabine, mean = 9.2 x 10(8) photons/s, versus combination, mean = 1.8 x 10(8) photons/s, difference = 7.4 x 10(8) photons/s; 95% CI = 4.5 x 10(8) to 1.0 x 10(9) photons/s; P<.001; MPanc-96: gemcitabine, mean = 4.1 x 10(9) photons/s, versus combination, mean = 2.0 x 10(9) photons/s, difference = 2.1 x 10(9) photons/s; 95% CI = 4.4 x 10(8) to 3.8 x 10(9) photons/s; P<.001).", "entity1": "S100P", "entity2": "gemcitabine", "span1": [79, 84], "span2": [511, 522]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12244": {"label": 8, "data": {"text": "The carboxylation of glutamic acid residues to gamma-carboxyglutamic acid (Gla) by the vitamin K-dependent gamma-glutamyl carboxylase (gamma-carboxylase) is an essential posttranslational modification required for the biological activity of a number of proteins, including proteins involved in blood coagulation and its regulation.", "entity1": "gamma-carboxylase", "entity2": "glutamic acid", "span1": [135, 152], "span2": [21, 34]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4333": {"label": 3, "data": {"text": "Suppression of Src/ERK and GSK-3/\u03b2-catenin signaling by pinosylvin inhibits the growth of human colorectal cancer cells.", "entity1": "GSK-3", "entity2": "pinosylvin", "span1": [27, 32], "span2": [56, 66]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1530": {"label": 3, "data": {"text": "The beta subunit has been cloned and shown to lower the K(m) of methionine adenosyltransferase II alpha2 (the MAT2A product) for methionine and to render the enzyme more susceptible to S-adenosylmethionine inhibition.", "entity1": "MAT2A", "entity2": "S-adenosylmethionine", "span1": [110, 115], "span2": [185, 205]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"2931": {"label": 0, "data": {"text": "AdSS from the thermophilic archaea, Methanocaldococcus jannaschii (MjAdSS) is 345 amino acids long against an average length of 430-457 amino acids for most mesophilic AdSS.", "entity1": "MjAdSS", "entity2": "amino acids", "span1": [67, 73], "span2": [82, 93]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1860": {"label": 3, "data": {"text": "Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase (DGAT).", "entity1": "DGAT", "entity2": "kurarinol", "span1": [253, 257], "span2": [73, 82]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12397": {"label": 3, "data": {"text": "Dexamethasone suppressed IL-11 gene transcription enhanced by PTH(1-34) without affecting \u0394FosB expression or Smad1 phosphorylation, and dexamethasone-GC receptor complex was bound to JunD, which forms heterodimers with \u0394FosB.", "entity1": "IL-11", "entity2": "Dexamethasone", "span1": [25, 30], "span2": [0, 13]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6542": {"label": 4, "data": {"text": "Probes were perfused with artificial cerebrospinal fluid containing nicotine, the specific alpha(4)beta(2*) nAChR agonist metanicotine, or nicotine plus nAChR antagonists and norepinephrine measured in the microdialysates.", "entity1": "alpha(4)beta(2*) nAChR", "entity2": "metanicotine", "span1": [91, 113], "span2": [122, 134]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2348": {"label": 2, "data": {"text": "GW9662, a PPARgamma antagonist, prevented (P < 0.01) the lutein-induced iNOS mRNA downregulation in HD11 cells.", "entity1": "iNOS", "entity2": "GW9662", "span1": [72, 76], "span2": [0, 6]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, 3, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9116": {"label": 1, "data": {"text": "The site at which phenoxybenzamine bound to calmodulin appears to be similar to that at which certain antipsychotic agents bind, since several of them, including penfluridol, pimozide and spiroperidol, prevented the binding of phenoxybenzamine to calmodulin.", "entity1": "calmodulin", "entity2": "penfluridol", "span1": [247, 257], "span2": [162, 173]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"632": {"label": 3, "data": {"text": "Taken together, these data demonstrated that PLA2 inhibitors BPB and AACOCF3 are robust inhibitors of IL-2 expression at both the mRNA and protein levels in murine splenocytes.", "entity1": "PLA2", "entity2": "AACOCF3", "span1": [45, 49], "span2": [69, 76]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11386": {"label": 1, "data": {"text": "In this sample of neuroleptic-refractory schizophrenic patients, olanzapine and clozapine showed a different pattern of occupancy of D2-like receptor despite a common lack of extrapyramidal side-effects.", "entity1": "D2-like receptor", "entity2": "clozapine", "span1": [133, 149], "span2": [80, 89]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1697": {"label": 3, "data": {"text": "BACKGROUND: Rivastigmine is a carbamate drug designed to inhibit both acetylcholinesterase and butyrylcholinesterase by reversibly covalently bonding to these enzymes.", "entity1": "acetylcholinesterase", "entity2": "carbamate", "span1": [70, 90], "span2": [30, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7801": {"label": 9, "data": {"text": "However, 4'G-RSV, but not 3G-RSV, induced SIRT1-dependent histone H3 deacetylation and SOD2 expression in mouse C2C12 skeletal myoblasts; as with RSV, SIRT1 knockdown blunted these effects.", "entity1": "histone H3", "entity2": "3G-RSV", "span1": [58, 68], "span2": [26, 32]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"10103": {"label": 3, "data": {"text": "The elevation in brain alanine levels could be explained, at least in part, by a time- and dose-dependent inhibitory effect of PLZ on alanine transaminase (ALA-T), although as with GABA the increases are higher than expected from the degree of enzyme inhibition produced.", "entity1": "ALA-T", "entity2": "PLZ", "span1": [156, 161], "span2": [127, 130]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"5576": {"label": 3, "data": {"text": "Some of these derivatives showed good inhibitory potency against two human CA isozymes involved in important physiological processes, CA I, and CA II, of the same order of magnitude as the clinically used drugs acetazolamide and methazolamide.", "entity1": "CA II", "entity2": "acetazolamide", "span1": [144, 149], "span2": [211, 224]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6975": {"label": 1, "data": {"text": "Recently, a G-protein-coupled receptor, termed GPR109A (HM74A in humans, PUMA-G in mice), was described and shown to mediate the nicotinic acid-induced antilipolytic effects in adipocytes.", "entity1": "PUMA-G", "entity2": "nicotinic acid", "span1": [73, 79], "span2": [129, 143]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14651": {"label": 8, "data": {"text": "Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.", "entity1": "Pro122Ser", "entity2": "cytarabine", "span1": [96, 105], "span2": [210, 220]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"12295": {"label": 1, "data": {"text": "Quercetin supplementation altered expression profiles of several lipid metabolism-related genes, including Fnta, Pon1, Pparg, Aldh1b1, Apoa4, Abcg5, Gpam, Acaca, Cd36, Fdft1, and Fasn, relative to those in HFD control mice.", "entity1": "Aldh1b1", "entity2": "Quercetin", "span1": [126, 133], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8788": {"label": 3, "data": {"text": "Treatment with CAPE decreased protein abundance of Akt, Akt1, Akt2, Akt3, phospho-Akt Ser473, phospho-Akt Thr 308, GSK3\u03b2, FOXO1, FOXO3a, phospho-FOXO1 Thr24, phospho-FoxO3a Thr32, NF-\u03baB, phospho-NF-\u03baB Ser536, Rb, phospho-Rb Ser807/811, Skp2, and cyclin D1, but increased cell cycle inhibitor p27Kip.", "entity1": "phospho-FoxO3a", "entity2": "CAPE", "span1": [158, 172], "span2": [15, 19]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3028": {"label": 1, "data": {"text": "Taxanes with affinities for microtubules well above their affinities for P-glycoprotein are shown not to be affected by multidrug resistance.", "entity1": "P-glycoprotein", "entity2": "Taxanes", "span1": [73, 87], "span2": [0, 7]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9044": {"label": 1, "data": {"text": "Benzodiazepine receptor binding of triazolobenzodiazepines in vivo: increased receptor number with low-dose alprazolam.", "entity1": "Benzodiazepine receptor", "entity2": "triazolobenzodiazepines", "span1": [0, 23], "span2": [35, 58]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13955": {"label": 2, "data": {"text": "However, both compounds have similar molecular mechanisms of neuroprotection in neuronal cell cultures and animal neurodegenerative models, indicating that the neuroprotective effect of rasagiline does not depend on inhibition of MAO-B, but rather is associated with the N-propargyl moiety, which promotes mitochondrial viability and stabilizes permeability transition by regulating Bcl-2 family proteins.", "entity1": "Bcl-2", "entity2": "N-propargyl", "span1": [383, 388], "span2": [271, 282]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1558": {"label": 5, "data": {"text": "Kynurenic acid (KA) is an endogenous glutamate receptor antagonist at the level of the different ionotropic glutamate receptors.", "entity1": "glutamate receptor", "entity2": "KA", "span1": [37, 55], "span2": [16, 18]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"14198": {"label": 1, "data": {"text": "In conclusion, these results suggest that CHOP may sensitize FRO ATC cells to SU5416 thereby inhibiting cell survival by modulating p21 and PI3K/Akt signal pathway.", "entity1": "Akt", "entity2": "SU5416", "span1": [145, 148], "span2": [78, 84]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3292": {"label": 3, "data": {"text": "Rasagiline is a novel, potent, and irreversible monoamine oxidase type B (MAO-B) inhibitor which has been approved for treatment of PD.", "entity1": "monoamine oxidase type B", "entity2": "Rasagiline", "span1": [48, 72], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3548": {"label": 2, "data": {"text": "These results suggest that LTD4 increases A\u03b2 peptide burden via activation of CysLT(1)R, which further affects APP levels and activity of \u03b2- and \u03b3-secretases via the NF-\u03baB pathway.", "entity1": "A\u03b2 peptide", "entity2": "LTD4", "span1": [42, 52], "span2": [27, 31]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5488": {"label": 1, "data": {"text": "Of the progestagens tested in this study, only norethinodrel displayed measurable but very low relative affinity for the oestrogen receptor in MCF-7 cells.", "entity1": "oestrogen receptor", "entity2": "norethinodrel", "span1": [121, 139], "span2": [47, 60]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8368": {"label": 1, "data": {"text": "The crystal structure of HSA complexed with fatty acid and acetyldiflunisal revealed that acetyldiflunisal binds to the IIA subdomain and that upon binding, it acetylates lysine 199.", "entity1": "HSA", "entity2": "acetyldiflunisal", "span1": [25, 28], "span2": [59, 75]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12565": {"label": 8, "data": {"text": "The drug had a potent cytotoxic effect on RIN cells expressing GLUT2, but had no effect on cells lacking GLUT2 expression, as indicated by histological analysis and measurement of the blood glucose levels of treated animals.", "entity1": "GLUT2", "entity2": "glucose", "span1": [63, 68], "span2": [190, 197]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3514": {"label": 1, "data": {"text": "TZD effects on osteoblast viability, oleic acid uptake, alkaline phosphatase and osteocalcin production are independent of their effects on aromatase.", "entity1": "alkaline phosphatase", "entity2": "TZD", "span1": [56, 76], "span2": [0, 3]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"2582": {"label": 8, "data": {"text": "CONCLUSIONS: These findings indicate that increased synthesis of histamine through up-regulation of HDC gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity.", "entity1": "HDC", "entity2": "histamine", "span1": [100, 103], "span2": [65, 74]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8119": {"label": 3, "data": {"text": "Both CE and E(2) alone increased DNA synthesis and reduced apoptosis with activation of MAPK, Akt, and p70S6K and up-regulation of antiapoptotic factors survivin, Bcl-2, and X-linked inhibitor of apoptosis protein, These effects could be completely blocked by BZA.", "entity1": "X-linked inhibitor of apoptosis protein", "entity2": "BZA", "span1": [174, 213], "span2": [260, 263]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9422": {"label": 0, "data": {"text": "PTP inhibition by hisphosphonates or vanadate was diminished by the metal chelating agent EDTA, or by the reducing agent dithiothreitol, suggesting that a metal ion and the oxidation of a cysteine residue are required for full inhibition.", "entity1": "PTP", "entity2": "cysteine", "span1": [0, 3], "span2": [188, 196]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13328": {"label": 3, "data": {"text": "Sulfasalazine (also as a representative of the salicylates) inhibited the diabetes-induced upregulation of several inflammatory gene products, which are regulated by NF-kappaB, including vascular cell adhesion molecule, intracellular adhesion molecule-1, inducible nitric oxide synthase, and cyclooxygenase-2 in whole-retinal lysate.", "entity1": "cyclooxygenase-2", "entity2": "Sulfasalazine", "span1": [292, 308], "span2": [0, 13]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"11849": {"label": 2, "data": {"text": "Furthermore, the up-regulation of IL-12 and TNF-\u03b1 was found in the procyanidin trimers-treated cells in the presence of OVA.", "entity1": "IL-12", "entity2": "procyanidin", "span1": [34, 39], "span2": [67, 78]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13803": {"label": 3, "data": {"text": "The most successful example of kinase blockers is Imatinib (Imatinib mesylate, Gleevec, STI571), the inhibitor of Bcr/Abl oncoprotein, which has become a first-line therapy for chronic myelogenous leukemia.", "entity1": "Abl", "entity2": "Gleevec", "span1": [118, 121], "span2": [79, 86]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3276": {"label": 3, "data": {"text": "Using a unique biosensor-based assay, trifluoperazine (TFP) was identified as an inhibitor that disrupts the S100A4/myosin-IIA interaction.", "entity1": "S100A4", "entity2": "TFP", "span1": [109, 115], "span2": [55, 58]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5666": {"label": 2, "data": {"text": "Therefore, matrine and oxymatrine may have the potential to cure LQT2 as a potassium channel activator by promoting hERG channel activation and increasing hERG channel expression.", "entity1": "hERG", "entity2": "matrine", "span1": [155, 159], "span2": [11, 18]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15911": {"label": 1, "data": {"text": "Estradiol replacement enhances cocaine-stimulated locomotion in female C57BL/6 mice through estrogen receptor alpha.", "entity1": "estrogen receptor alpha", "entity2": "cocaine", "span1": [92, 115], "span2": [31, 38]}, "weak_labels": [-1, 0, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9585": {"label": 3, "data": {"text": "All three compounds displayed antagonistic properties against oxytocin in vitro, with carbetocin being the strongest inhibitor (pA2 = 8.21) and carbetocin metabolite II (pA2 = 8.01) being stronger than carbetocin metabolite I (pA2 = 7.81).", "entity1": "oxytocin", "entity2": "carbetocin", "span1": [62, 70], "span2": [86, 96]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2179": {"label": 0, "data": {"text": "Furthermore, tPA induced rapid tyrosine phosphorylation on the beta subunit of LRP-1, which was followed by the activation of Mek1 and its downstream Erk-1 and -2.", "entity1": "LRP-1", "entity2": "tyrosine", "span1": [79, 84], "span2": [31, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7810": {"label": 0, "data": {"text": "Hydrophobic amino acids in the hinge region of the 5A apolipoprotein mimetic peptide are essential for promoting cholesterol efflux by the ABCA1 transporter.", "entity1": "5A apolipoprotein", "entity2": "amino acids", "span1": [51, 68], "span2": [12, 23]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"2168": {"label": 0, "data": {"text": "Binding sites for hERG blockers have been mapped within the inner cavity of the channel and include aromatic residues in the S6 helix (Tyr-652, Phe-656) and residues in the pore helix (Thr-623, Ser-624, Val-625).", "entity1": "hERG", "entity2": "Val", "span1": [18, 22], "span2": [203, 206]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13215": {"label": 1, "data": {"text": "Triflusal, a selective cyclooxygenase-2, and its active metabolite 3-hydroxy-4-trifluoromethylbenzoic acid may inhibit apoptosis and inflammation after cerebral ischemia.", "entity1": "cyclooxygenase-2", "entity2": "Triflusal", "span1": [23, 39], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2647": {"label": 8, "data": {"text": "LDH is responsible for pyruvate conversion to lactate through glycolysis.", "entity1": "LDH", "entity2": "lactate", "span1": [0, 3], "span2": [46, 53]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1]},
	"3418": {"label": 2, "data": {"text": "The treatment with arsenic exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine).", "entity1": "aspartate aminotransferase", "entity2": "arsenic", "span1": [142, 168], "span2": [19, 26]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7744": {"label": 3, "data": {"text": "PURPOSE: XL184 (cabozantinib) is a potent inhibitor of MET, vascular endothelial growth factor receptor 2 (VEGFR2), and RET, with robust antiangiogenic, antitumor, and anti-invasive effects in preclinical models.", "entity1": "MET", "entity2": "XL184", "span1": [55, 58], "span2": [9, 14]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9041": {"label": 4, "data": {"text": "It is suggested that all the additional actions of bevantolol can be attributed to a partial agonist action on alpha-adrenoceptors.", "entity1": "alpha-adrenoceptors", "entity2": "bevantolol", "span1": [111, 130], "span2": [51, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5136": {"label": 3, "data": {"text": "In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, showed a partial suppressive effect of 5HHMF on LPS-induced NO production.", "entity1": "HO-1", "entity2": "zinc protoporphyrin", "span1": [52, 56], "span2": [13, 32]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"11746": {"label": 0, "data": {"text": "The Ves a 1 structure, which is composed of seven \u03b1-helixes and eleven \u03b2-strands, contains the \u03b2-strand/\u025bSer/\u03b1-helix structural motif, which contains the Gly-X-Ser-X-Gly consensus sequence.", "entity1": "Ves a 1", "entity2": "Gly", "span1": [4, 11], "span2": [166, 169]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14337": {"label": 3, "data": {"text": "Finally, DMF suppressed unilateral ureteral obstruction (UUO)-induced renal fibrosis and alpha-SMA, fibronectin and type 1 collagen expression in the obstructed kidneys from UUO mice, along with increased and decreased expression of Nrf2 and phospho-Smad3, respectively.", "entity1": "type 1 collagen", "entity2": "DMF", "span1": [116, 131], "span2": [9, 12]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8865": {"label": 2, "data": {"text": "In the present study, using in vitro Th17 differentiation model, we examined effects of AhR activation by indoxyl 3-sulfate (I3S), a uremic toxin, on Th17 differentiation and investigated underlying mechanisms.", "entity1": "AhR", "entity2": "I3S", "span1": [88, 91], "span2": [125, 128]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2199": {"label": 3, "data": {"text": "Our results have shown that MMP-9 messenger ribonucleic acid (mRNA) expression was inhibited by doxycycline starting at 10 mg/kg/day (P<0.02).", "entity1": "MMP-9", "entity2": "doxycycline", "span1": [28, 33], "span2": [96, 107]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3009": {"label": 3, "data": {"text": "Inhibition of dipeptidyl peptidase-IV (DPP-IV) by atorvastatin.", "entity1": "DPP-IV", "entity2": "atorvastatin", "span1": [39, 45], "span2": [50, 62]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"864": {"label": 3, "data": {"text": "Depletion of putrescine, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "entity1": "ODC", "entity2": "DL-alpha-difluoromethylornithine", "span1": [143, 146], "span2": [53, 85]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9052": {"label": 1, "data": {"text": "In vitro binding affinities of chlorpromazine, fluphenazine, levomepromazine, perphenazine and some of their metabolites for dopamine D2 receptors, alpha 1- and alpha 2 adrenoceptors in rat brain were previously reported from our laboratories.", "entity1": "dopamine D2 receptors", "entity2": "levomepromazine", "span1": [125, 146], "span2": [61, 76]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4610": {"label": 3, "data": {"text": "Pretreatment of rats with glutathione (GSH) depletors (phorone or BSO) delayed the elimination of DMAs(V) and the accumulation of RBC-bound DMAs, whereas the indirect methyltransferase inhibitor periodate-oxidized adenosine was without effect.", "entity1": "methyltransferase", "entity2": "adenosine", "span1": [167, 184], "span2": [214, 223]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9525": {"label": 3, "data": {"text": "Dihydropyridines (DHPs) block L-type Ca2+ channels more potently at depolarized membrane potentials, consistent with high affinity binding to the inactivated state.", "entity1": "L-type Ca2+ channels", "entity2": "Dihydropyridines", "span1": [30, 50], "span2": [0, 16]}, "weak_labels": [-1, -1, -1, 1, -1, 1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5192": {"label": 3, "data": {"text": "Treatment of A549 and H1299 cells with dioscin caused a dose-dependent increase in ERK1/2 and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR.", "entity1": "mTOR", "entity2": "dioscin", "span1": [197, 201], "span2": [39, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9453": {"label": 1, "data": {"text": "The EP3 receptor showed the broadest binding profile, and bound sulprostone, M&B-28767, GR63799X, 11-deoxy-PGE1, 16,16-dimethyl-PGE2 and 17-phenyl-PGE2, in addition to PGE2 and PGE1, with Ki values of 0.6-3.7 nM.", "entity1": "EP3", "entity2": "sulprostone", "span1": [4, 7], "span2": [64, 75]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9502": {"label": 3, "data": {"text": "The sodium channel-blocking action of cocaine per se does not appear to be involved in the rapid pressor response to cocaine.", "entity1": "sodium channel", "entity2": "cocaine", "span1": [4, 18], "span2": [38, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9692": {"label": 1, "data": {"text": "Pretreatment with the 5-HT1A antagonist WAY-100,635 (10 micrograms/kg i.v.) prevented the ziprasidone-induced inhibition; the same dose of WAY-100,635 had little effect on the inhibition produced by clozapine and olanzapine.", "entity1": "5-HT1A", "entity2": "clozapine", "span1": [22, 28], "span2": [199, 208]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"844": {"label": 5, "data": {"text": "This selectivity could, in part, account for the more favorable clinical profile of felbamate in comparison with NMDA receptor antagonists that do not show subunit selectivity.", "entity1": "NMDA receptor", "entity2": "felbamate", "span1": [113, 126], "span2": [84, 93]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"6398": {"label": 1, "data": {"text": "Study of the additional subjects revealed that quetiapine does give rise to transiently high (58%-64%) D2 occupancy 2 to 3 hours after a single dose that then decreases to minimal levels in 12 hours.", "entity1": "D2", "entity2": "quetiapine", "span1": [103, 105], "span2": [47, 57]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3794": {"label": 3, "data": {"text": "Moreover, use of the pharmacological AMP-activated protein kinase (AMPK) inhibitor compound C revealed that AMPK is essential for suppressing SREBP-1c expression in phillyrin-treated cells.", "entity1": "AMP-activated protein kinase", "entity2": "compound C", "span1": [37, 65], "span2": [83, 93]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5092": {"label": 1, "data": {"text": "Aldosterone regulates Na(+) transport in the distal nephron through multiple mechanisms that include the transcriptional control of epithelial sodium channel (ENaC) and Na(+)/K(+)-ATPase subunits.", "entity1": "ENaC", "entity2": "Aldosterone", "span1": [159, 163], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"11416": {"label": 1, "data": {"text": "Comparison of the crystal structures of UDP-Gal- and UDP-Glc-bound beta4Gal-T1 reveals that the O4 hydroxyl group in both Gal and Glc moieties forms a hydrogen bond with the side chain carboxylate group of Glu317.", "entity1": "beta4Gal-T1", "entity2": "UDP-Glc", "span1": [67, 78], "span2": [53, 60]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15622": {"label": 3, "data": {"text": "Furthermore, galangin attenuated IgE-mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue.", "entity1": "histamine receptor 1", "entity2": "galangin", "span1": [98, 118], "span2": [13, 21]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15373": {"label": 2, "data": {"text": "The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, all-trans retinoic acid (atRA), which regulates the expression of a battery of target genes through several families of nuclear receptors (RARs, RXRs and PPAR\u03b2/\u03b4), polymorphic retinoic acid (RA) response elements and multiple coregulators.", "entity1": "polymorphic retinoic acid (RA) response elements", "entity2": "atRA", "span1": [246, 294], "span2": [107, 111]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4487": {"label": 4, "data": {"text": "Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the G protein-coupled receptor agonist acetylcholine (ACh) and by cyclopiazonic acid (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial SERCA pump.", "entity1": "G protein-coupled receptor", "entity2": "acetylcholine", "span1": [176, 202], "span2": [211, 224]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10161": {"label": 1, "data": {"text": "ICI 182,780 (fulvestrant) (Faslodex) and ICI 164,384 are competitive inhibitors of estrogen by binding to the estrogen receptor (ER).", "entity1": "ER", "entity2": "Faslodex", "span1": [129, 131], "span2": [27, 35]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5974": {"label": 3, "data": {"text": "Phenol oxidase inhibitors such as phenylthiourea, potassium cyanide, and sodium azide inhibited the reaction drastically, suggesting the participation of the active site copper of the enzyme in the catalysis.", "entity1": "Phenol oxidase", "entity2": "potassium cyanide", "span1": [0, 14], "span2": [50, 67]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"11415": {"label": 1, "data": {"text": "Comparison of the crystal structures of UDP-Gal- and UDP-Glc-bound beta4Gal-T1 reveals that the O4 hydroxyl group in both Gal and Glc moieties forms a hydrogen bond with the side chain carboxylate group of Glu317.", "entity1": "beta4Gal-T1", "entity2": "UDP-Gal", "span1": [67, 78], "span2": [40, 47]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9644": {"label": 3, "data": {"text": "Exposure of LNCaP cells to estramustine for 24 hr caused transcriptional inhibition of PSA in a concentration-dependent manner.", "entity1": "PSA", "entity2": "estramustine", "span1": [87, 90], "span2": [27, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1927": {"label": 8, "data": {"text": "Carnitine acetyltransferases (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to acetylcarnitine and free CoA.", "entity1": "CrAT", "entity2": "acetyl-CoA", "span1": [30, 34], "span2": [74, 84]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 8, -1]},
	"12135": {"label": 1, "data": {"text": "In contrast to UCP-3, UCP-2 mRNA levels were only slightly modified by bezafibrate in adipocytes.", "entity1": "UCP-2", "entity2": "bezafibrate", "span1": [22, 27], "span2": [71, 82]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14615": {"label": 8, "data": {"text": "Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.", "entity1": "CDA", "entity2": "2',2'-difluorodeoxyuridine", "span1": [34, 37], "span2": [255, 281]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"8890": {"label": 9, "data": {"text": "The potent anabolic effects of the beta 2-adrenoceptor agonist clenbuterol on skeletal muscle have been reported to be independent of actions on beta-adrenoceptors.", "entity1": "beta-adrenoceptors", "entity2": "clenbuterol", "span1": [145, 163], "span2": [63, 74]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12137": {"label": 2, "data": {"text": "To mechanistically evaluate this regional selectivity, we assessed cyclo-oxygenase-2 (COX-2) expression in the uninvolved mucosa and demonstrated a 3- to 4-fold excess in the distal relative to the proximal bowel in both MIN mice and AOM-treated rats.", "entity1": "cyclo-oxygenase-2", "entity2": "AOM", "span1": [67, 84], "span2": [234, 237]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10474": {"label": 1, "data": {"text": "BACKGROUND: The norepinephrine transporter (NET) is a high-affinity transporter for catecholamines.", "entity1": "norepinephrine transporter", "entity2": "catecholamines", "span1": [16, 42], "span2": [84, 98]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"15964": {"label": 2, "data": {"text": "Collectively, our data indicate that OHT contributes to the production of proteolyzed cyclin E via GPR30 with augmented migration in MCF-7 cells.", "entity1": "cyclin E", "entity2": "OHT", "span1": [86, 94], "span2": [37, 40]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"9499": {"label": 3, "data": {"text": "At nonconvulsant doses, the sodium channel blockers acetylprocainamide, dibucaine, dyclonine, prilocaine, proparacaine, quinidine, and tetracaine produced a small pressor response or no increase in BP.", "entity1": "sodium channel", "entity2": "proparacaine", "span1": [28, 42], "span2": [106, 118]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"14715": {"label": 3, "data": {"text": "Furthermore, insulin-stimulated T-I cell proliferation and the expression of cell cycle regulatory proteins CDK4, CCND3 and PCNA were also blocked by rapamycin.", "entity1": "PCNA", "entity2": "rapamycin", "span1": [124, 128], "span2": [150, 159]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5046": {"label": 1, "data": {"text": "These illnesses are a result of saxitoxin's ability to bind to the voltage-gated sodium channel, blocking the passage of nerve impulses and leading to death via respiratory paralysis.", "entity1": "voltage-gated sodium channel", "entity2": "saxitoxin", "span1": [67, 95], "span2": [32, 41]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7287": {"label": 3, "data": {"text": "PFD leads to a reduction of TGF-beta2 mRNA levels and of the mature TGF-beta2 protein due to decreased expression and direct inhibition of the TGF-beta pro-protein convertase furin.", "entity1": "TGF-beta", "entity2": "PFD", "span1": [143, 151], "span2": [0, 3]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1]},
	"7341": {"label": 8, "data": {"text": "Na+-Dependent transmembrane transport of small neutral amino acids, such as glutamine and alanine, is mediated, among others, by the neutral amino acid transporters of the solute carrier 1 [SLC1, alanine serine cysteine transporter 1 (ASCT1), and ASCT2] and SLC38 families [sodium-coupled neutral amino acid transporter 1 (SNAT1), SNAT2, and SNAT4].", "entity1": "solute carrier 1", "entity2": "alanine", "span1": [172, 188], "span2": [90, 97]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"15529": {"label": 3, "data": {"text": "In this setting, S-nitrosocysteine (10 \u03bcm) effectively blocked the Trx-mediated regeneration of oxidized Prx1.", "entity1": "Trx", "entity2": "S-nitrosocysteine", "span1": [67, 70], "span2": [17, 34]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"96": {"label": 3, "data": {"text": "Catecholamines (adrenaline, noradrenaline and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase (phenylalanine hydroxylase, EC 1.14.16.1).", "entity1": "phenylalanine hydroxylase", "entity2": "Catecholamines", "span1": [112, 137], "span2": [0, 14]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5079": {"label": 2, "data": {"text": "In addition to CYP2B6, anisomycin co-treatment potentiated an increase in CYP2A7 and CYP2C9 mRNAs but not CYP3A4 or UDP-glucuronosyltransferase 1A1 mRNAs.", "entity1": "CYP2A7", "entity2": "anisomycin", "span1": [74, 80], "span2": [23, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9676": {"label": 8, "data": {"text": "We find that FP causes a decrease in stimulated eosinophil secretion of LTC4 that is regulated by phospholipase A2 (PLA2).", "entity1": "PLA2", "entity2": "LTC4", "span1": [116, 120], "span2": [72, 76]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2249": {"label": 3, "data": {"text": "BACKGROUND: Since the introduction of the first cholinesterase inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, galantamine and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase.", "entity1": "acetylcholinesterase", "entity2": "rivastigmine", "span1": [492, 512], "span2": [197, 209]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2136": {"label": 1, "data": {"text": "Thiazolidinediones are a new class of anti-diabetic agents which increase insulin sensitivity by binding to the peroxisome proliferator-activated receptor gamma (PPAR(gamma)) and stimulating the expression of insulin-responsive genes involved in glucose and lipid metabolism.", "entity1": "peroxisome proliferator-activated receptor gamma", "entity2": "Thiazolidinediones", "span1": [112, 160], "span2": [0, 18]}, "weak_labels": [-1, -1, -1, 1, -1, -1, 2, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12546": {"label": 1, "data": {"text": "From these results, it is proposed that tyrosine hydroxylase activity determines p-HPAA concentrations by regulating p-tyrosine availability.", "entity1": "tyrosine hydroxylase", "entity2": "p-HPAA", "span1": [40, 60], "span2": [81, 87]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"16062": {"label": 8, "data": {"text": "Simvastatin and lovastatin metabolized through CYP3A have the highest potency for drug-drug interaction with potent CYP3A inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the hepatitis C virus (HCV) PI, telaprevir or boceprevir, and therefore their coadministration is contraindicated.", "entity1": "CYP3A", "entity2": "Simvastatin", "span1": [47, 52], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11572": {"label": 8, "data": {"text": "zRetSat A also saturated the 13-14 or 7-8 double bonds of all-trans-3,4-didehydroretinol (vitamin A2), a second endogenous form of vitamin A in zebrafish.", "entity1": "zRetSat A", "entity2": "vitamin A2", "span1": [0, 9], "span2": [90, 100]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4057": {"label": 3, "data": {"text": "In this study, focus was given to evaluate the ability of neoechinulin A, an indole alkaloid isolated from marine-derived Microsporum sp., to attenuate microglial activation by oligomeric amyloid-\u03b2 1-42 (A\u03b242).", "entity1": "A\u03b242", "entity2": "indole", "span1": [204, 208], "span2": [77, 83]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"787": {"label": 9, "data": {"text": "Specifically, aniracetam, which potentiates wild-type AMPA receptors, is ineffective on the non-desensitizing GluR3(L507Y) mutant, but has synergistic effects with lithium on wild-type receptors.", "entity1": "L507Y", "entity2": "aniracetam", "span1": [116, 121], "span2": [14, 24]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1101": {"label": 3, "data": {"text": "Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.", "entity1": "acetylcholinesterase", "entity2": "tacrine", "span1": [242, 262], "span2": [111, 118]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2987": {"label": 1, "data": {"text": "Catalytic-site affinities for cGMP, vardenafil, sildenafil, tadalafil, or 3-isobutyl-1-methylxanthine (IBMX) were respectively weakened 14-, 123-, 30-, 51-, and 43-fold for Y612A; 63-, 511-, 43-, 95- and 61-fold for Q817A; and 59-, 448-, 71-, 137-, and 93-fold for F820A.", "entity1": "F820A", "entity2": "vardenafil", "span1": [265, 270], "span2": [36, 46]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2458": {"label": 9, "data": {"text": "The adenosine triphosphate binding cassette (ABC)-transporter ABCC2 (MRP2/cMOAT) can mediate resistance against the commonly used anticancer drugs cisplatin and paclitaxel.", "entity1": "cMOAT", "entity2": "cisplatin", "span1": [74, 79], "span2": [147, 156]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"13756": {"label": 9, "data": {"text": "Bosutinib did not inhibit KIT or platelet-derived growth factor receptor, but prominently targeted the apoptosis-linked STE20 kinases.", "entity1": "KIT", "entity2": "Bosutinib", "span1": [26, 29], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"10285": {"label": 3, "data": {"text": "An inhibitor of type B monoamine oxidase (MAO-B), (-)deprenyl (selegiline), was reported to have neuroprotective activity, but clinical trials failed to confirm it.", "entity1": "type B monoamine oxidase", "entity2": "(-)deprenyl", "span1": [16, 40], "span2": [50, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4492": {"label": 3, "data": {"text": "Add-on therapy with the DPP-4 inhibitor sitagliptin improves glycemic control in insulin-treated Japanese patients with type 2 diabetes mellitus.", "entity1": "DPP-4", "entity2": "sitagliptin", "span1": [24, 29], "span2": [40, 51]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7958": {"label": 3, "data": {"text": "Here, we compared the effects of a dimeric PSD-95 inhibitor, UCCB01-125, and the NMDAR antagonist, MK-801, on mechanical hypersensitivity in the complete Freund's adjuvant (CFA) model of inflammatory pain.", "entity1": "PSD-95", "entity2": "UCCB01-125", "span1": [43, 49], "span2": [61, 71]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7667": {"label": 3, "data": {"text": "Some of these structurally related compounds have a very different behavior against the widespread isozyme CA II, with chlorthalidone, trichloromethiazide, and furosemide being efficient inhibitors against CA II (K(I)s of 65-138 nM), whereas indapamide is a much weaker one (K(I) of 2520 nM).", "entity1": "CA II", "entity2": "chlorthalidone", "span1": [206, 211], "span2": [119, 133]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9832": {"label": 3, "data": {"text": "Moreover, geldanamycin decreases the amount and phosphorylation of Lck and Raf-1 kinases and prevents activation of the extracellular signal regulated kinase (ERK)-2 kinase.", "entity1": "Raf-1", "entity2": "geldanamycin", "span1": [75, 80], "span2": [10, 22]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12156": {"label": 3, "data": {"text": "We sought to assess the effects of the angiotensin type 1 (AT1) receptor blocker eprosartan on HRV and BRG.", "entity1": "angiotensin type 1 (AT1) receptor", "entity2": "eprosartan", "span1": [39, 72], "span2": [81, 91]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9850": {"label": 1, "data": {"text": "Salicylates do not promote dissociation of (125)I-ET-1 ETB receptor complexes.", "entity1": "ET-1", "entity2": "(125)I", "span1": [50, 54], "span2": [43, 49]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"13569": {"label": 1, "data": {"text": "A humanized antibody to HER2/neu, trastuzumab, is now FDA approved for the treatment of early stage, HER2/neu overexpressing breast cancer sequenced with chemotherapy including doxorubicin, cyclophosphamide, and paclitaxel.", "entity1": "HER2", "entity2": "cyclophosphamide", "span1": [101, 105], "span2": [190, 206]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6561": {"label": 3, "data": {"text": "Molecular models show that the PDE3 inhibitors cilostazol and milrinone share some of common residues but interact with distinct residues at the active site, suggesting that selective inhibitors can be designed with flexible size against PDE3 active site.", "entity1": "PDE3", "entity2": "cilostazol", "span1": [31, 35], "span2": [47, 57]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1990": {"label": 5, "data": {"text": "Mibefradil is a T-type Ca2+ channel antagonist with reported cross-reactivity with other classes of ion channels, including K+, Cl-, and Na+ channels.", "entity1": "T-type Ca2+ channel", "entity2": "Mibefradil", "span1": [16, 35], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4723": {"label": 3, "data": {"text": "TCDD inhibition of canonical wnt signaling disrupts prostatic bud formation in mouse urogenital sinus.", "entity1": "wnt", "entity2": "TCDD", "span1": [29, 32], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14820": {"label": 1, "data": {"text": "In early pregnancy, there were no significant differences in insulin sensitivity (insulin sensitivity index derived from OGTT [ISOGTT] and homeostasis model assessment for insulin resistance [HOMA-IR]) and insulin secretion (a ratio of the total area-under-the-insulin-curve to the total area-under-the-glucose-curve [AUCins/glu] and insulinogenic index [IGI]) between the NGT and late-onset GDM groups.", "entity1": "insulin", "entity2": "glucose", "span1": [61, 68], "span2": [303, 310]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11938": {"label": 3, "data": {"text": "To further our understanding of how fisetin negatively regulates mTORC1 signaling, we analyzed the phosphorylation of S6K1, mTOR and Akt in fisetin-treated TSC2-knockdown cells.", "entity1": "mTORC1", "entity2": "fisetin", "span1": [65, 71], "span2": [36, 43]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7616": {"label": 3, "data": {"text": "CONCLUSIONS: Lapatinib is a dual inhibitor of the EGFR and HER2 tyrosine kinases.", "entity1": "tyrosine kinases", "entity2": "Lapatinib", "span1": [64, 80], "span2": [13, 22]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1327": {"label": 9, "data": {"text": "Eprosartan is not metabolized by cytochrome P450 enzymes and therefore has a low potential for metabolic drug interactions, which may be of importance when treating the elderly and patients on multiple drugs.", "entity1": "cytochrome P450", "entity2": "Eprosartan", "span1": [33, 48], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"10561": {"label": 3, "data": {"text": "Irbesartan may have antiatherosclerotic properties beyond those expected from blood pressure lowering per se: this AT1-blocker decreases the vascular oxidative stress and prevents the procoagulant as well as the pro-inflammatory effects of angiotensin II.", "entity1": "angiotensin II", "entity2": "Irbesartan", "span1": [240, 254], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12504": {"label": 8, "data": {"text": "The results suggest that individuals with high Vmax beta 2-ADH and deficient in low-Km mitochondrial ALDH2, accounting for approximately 45% of the Chinese population, may end up with acetaldehyde accumulation during alcohol consumption, rendering them vulnerable to tissue injury caused by this highly reactive and toxic metabolite.", "entity1": "beta 2-ADH", "entity2": "alcohol", "span1": [52, 62], "span2": [217, 224]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"262": {"label": 0, "data": {"text": "In contrast, the Ala-->Gly replacement has less impact in protecting the chloride channel from the action of insecticidal blockers.", "entity1": "chloride channel", "entity2": "Gly", "span1": [73, 89], "span2": [23, 26]}, "weak_labels": [-1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6963": {"label": 5, "data": {"text": "Maraviroc inhibited binding of [125I]-MIP-1beta to CCR5 from macaque and human with similar potency (IC50 = 17.50 +/- 1.24 nM and 7.18 +/- 0.93 nM, respectively) and antagonised MIP-1beta induced intracellular calcium release mediated through CCR5 from macaque and human with similar potency (IC50 = 17.50 +/- 3.30 nM and 12.07 +/- 1.89, respectively).", "entity1": "CCR5", "entity2": "Maraviroc", "span1": [243, 247], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6599": {"label": 4, "data": {"text": "Although only clozapine and ziprasidone are directly acting 5-HT(1A) agonists, WAY100635, a selective 5-HT(1A) antagonist, partially attenuates these atypical APD-induced increases in cortical DA release that may be due to combined 5-HT(2A) and D(2) blockade.", "entity1": "5-HT(1A)", "entity2": "clozapine", "span1": [60, 68], "span2": [14, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9847": {"label": 8, "data": {"text": "gamma-Butyrobetaine hydroxylase catalyse the last step in carnitine biosynthesis, the formation of L-carnitine from gamma-butyrobetaine, a reaction dependent on Fe2+, alpha-ketoglutarate, ascorbate and oxygen.", "entity1": "gamma-Butyrobetaine hydroxylase", "entity2": "gamma-butyrobetaine", "span1": [0, 31], "span2": [116, 135]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"15861": {"label": 0, "data": {"text": "Molecular docking studies were performed with Human Serum Albumin (HSA: PDB 1E78), showing binding pattern with amino acid residues Arg218, Arg222 and Lys444, identifies the ligand-HSA interaction for the transportation affinity of the ligand at the specific site of the target.", "entity1": "Human Serum Albumin", "entity2": "Arg", "span1": [46, 65], "span2": [140, 143]}, "weak_labels": [0, -1, -1, 1, 1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"13323": {"label": 3, "data": {"text": "Oral aspirin (as a representative of the salicylate family) inhibited diabetes-induced increase in NF-kappaB DNA-binding affinity in electrophoretic mobility shift assay and transcription factor array in nuclear extract isolated from whole retina.", "entity1": "NF-kappaB", "entity2": "salicylate", "span1": [99, 108], "span2": [41, 51]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, 2, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"411": {"label": 1, "data": {"text": "The affinity estimate for prazosin on human prostate was lower than the corresponding binding affinity determined at alpha 1A adrenoceptors and RS 17053 was a very weak antagonist on human prostate (pA2 = 6.0) relative to the high affinity (pKi = 8.6) determined at cloned human alpha 1A adrenoceptors.", "entity1": "human alpha 1A adrenoceptors", "entity2": "RS 17053", "span1": [273, 301], "span2": [144, 152]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8971": {"label": 5, "data": {"text": "Using the alpha 1-adrenoceptor subtype-selective antagonists chlorethylclonidine (CEC), WB4101, and 5-methyl-urapidil, we have examined the possible heterogeneity in the alpha 1-adrenoceptor populations in rabbit aorta.", "entity1": "alpha 1-adrenoceptor", "entity2": "chlorethylclonidine", "span1": [10, 30], "span2": [61, 80]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10990": {"label": 3, "data": {"text": "Tyrosine kinase inhibitors are quinazoline-derived, low molecular weight synthetic molecules that can block the intracellular tyrosine kinase domain of several receptors, including EGFR, Erb2, and vascular endothelial growth factor receptor, and thereby inhibit ligand-induced receptor phosphorylation and abrogate the biologic effect of EGFR signaling.", "entity1": "Tyrosine kinase", "entity2": "quinazoline", "span1": [0, 15], "span2": [31, 42]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1319": {"label": 3, "data": {"text": "Disposition of a specific cyclooxygenase-2 inhibitor, valdecoxib, in human.", "entity1": "cyclooxygenase-2", "entity2": "valdecoxib", "span1": [26, 42], "span2": [54, 64]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5393": {"label": 3, "data": {"text": "In the IB-MECA group, \u03b1-amylase activity was decreased with statistically high significance compared to group I.", "entity1": "\u03b1-amylase", "entity2": "IB-MECA", "span1": [22, 31], "span2": [7, 14]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14911": {"label": 8, "data": {"text": "FMO3 overexpression in mice significantly increases plasma TMAO levels while silencing FMO3 decreases TMAO levels.", "entity1": "FMO3", "entity2": "TMAO", "span1": [0, 4], "span2": [59, 63]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4120": {"label": 1, "data": {"text": "Key marker of diabetes in cells is the insulin dependent glucose transporter-4 (Glut-4) which also responds to exogenous chemicals, and is over expressed up to 5- and 4-fold, by Tinospora cordifolia and palmatine, respectively.", "entity1": "Glut-4", "entity2": "palmatine", "span1": [80, 86], "span2": [203, 212]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"3414": {"label": 3, "data": {"text": "Transfection of the brain cDNA into COS-1 cells resulted in transporter activity that was blocked by the VMAT inhibitor reserpine and a proton ionophore, but not by tetrabenazine, which has a high affinity for VMAT-2.", "entity1": "VMAT", "entity2": "reserpine", "span1": [105, 109], "span2": [120, 129]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, 9]},
	"171": {"label": 1, "data": {"text": "The most potent compound, D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid (lorglumide, CR 1409), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent CCK antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini.", "entity1": "CCK receptors", "entity2": "lorglumide", "span1": [162, 175], "span2": [100, 110]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"67": {"label": 4, "data": {"text": "While there is considerable indirect evidence to implicate histamine in the pathogenesis of asthma, a critical evaluation of H1-receptor antagonism in this condition has, until recently, proved difficult, as many of the early H1-receptor antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity.", "entity1": "H1-receptor", "entity2": "histamine", "span1": [125, 136], "span2": [59, 68]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9170": {"label": 8, "data": {"text": "Chromatographic analysis of the metabolism of 14C-labeled arachidonic acid in this system revealed that PB-dependent inactivation of PHS is markedly increased in the presence of 100 microM H2O2.", "entity1": "PHS", "entity2": "14C-labeled arachidonic acid", "span1": [133, 136], "span2": [46, 74]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6268": {"label": 3, "data": {"text": "In vitro and in vivo studies have shown that argatroban has advantages over heparin for the inhibition of clot-bound thrombin and for the enhancement of thrombolysis with TPA.", "entity1": "thrombin", "entity2": "argatroban", "span1": [117, 125], "span2": [45, 55]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5661": {"label": 2, "data": {"text": "Long-term treatment with 1 \u03bcM matrine or oxymatrine increased expression of the hERG protein and rescued the hERG surface expression disrupted by As(2)O(3).", "entity1": "hERG", "entity2": "oxymatrine", "span1": [109, 113], "span2": [41, 51]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12995": {"label": 1, "data": {"text": "The phenylmorpholines, of which amorolfine is the sole representative in human therapy, affect two targets in the ergosterol pathway: Erg24p (delta 14 reductase) and Erg2p (delta 8-delta 7 isomerase).", "entity1": "delta 8-delta 7 isomerase", "entity2": "phenylmorpholines", "span1": [173, 198], "span2": [4, 21]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8145": {"label": 2, "data": {"text": "Increased urinary excretion of albumin, hemopexin, transferrin and VDBP correlates with chronic sensitization to gentamicin nephrotoxicity in rats.", "entity1": "albumin", "entity2": "gentamicin", "span1": [31, 38], "span2": [113, 123]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8206": {"label": 3, "data": {"text": "Ruxolitinib is a small-molecule inhibitor\u00a0of JAK1 and JAK2 and recently became the first drug approved by the United States Food and Drug Administration for the treatment of symptomatic intermediate- or high-risk myelofibrosis.", "entity1": "JAK2", "entity2": "Ruxolitinib", "span1": [54, 58], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5368": {"label": 1, "data": {"text": "Potent and selective: The unique nature of the ATP binding pocket structure of Pim family protein kinases (PKs) was used for the development of bisubstrate inhibitors and a fluorescent probe with sub-nanomolar affinity.", "entity1": "PKs", "entity2": "ATP", "span1": [107, 110], "span2": [47, 50]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"3037": {"label": 5, "data": {"text": "EP(1) and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth.", "entity1": "EP(1)", "entity2": "ONO-8713", "span1": [0, 5], "span2": [37, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1034": {"label": 1, "data": {"text": "Clinical effects of pranlukast, an oral leukotrieneleukotriene receptor antagonist, in mild-to-moderate asthma: a 4 week randomized multicentre controlled trial.", "entity1": "leukotriene receptor", "entity2": "leukotriene", "span1": [51, 71], "span2": [40, 51]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13505": {"label": 6, "data": {"text": "These data indicate that vecuronium, gallamine and pancuronium interact with an allosteric site on the muscarinic M2 receptor (located on the heart) and this may explain some of their cardiac side effects.", "entity1": "muscarinic M2 receptor", "entity2": "vecuronium", "span1": [103, 125], "span2": [25, 35]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1]},
	"8695": {"label": 8, "data": {"text": "Among the possible transporters involved in the uptake of Cd(2+) and Mn(2+), the expression of ZIP8 (Zrt-, Irt-related protein 8), encoded by Slc39a8, showed a marked suppression in both RBL-Cdr and RBL-Mnr cells.", "entity1": "Slc39a8", "entity2": "Mn(2+)", "span1": [142, 149], "span2": [69, 75]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"13713": {"label": 5, "data": {"text": "Irbesartan (Aprovel, Avapro, Irbetan, Karvea), an angiotensin II receptor type 1 antagonist, is approved in many countries worldwide for the treatment of hypertension.", "entity1": "angiotensin II receptor type 1", "entity2": "Irbesartan", "span1": [50, 80], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5254": {"label": 3, "data": {"text": "Mechanisms of Glucose Lowering of Dipeptidyl Peptidase-4 Inhibitor Sitagliptin When Used Alone or With Metformin in Type 2 Diabetes: A double-tracer study.", "entity1": "Dipeptidyl Peptidase-4", "entity2": "Sitagliptin", "span1": [34, 56], "span2": [67, 78]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13333": {"label": 9, "data": {"text": "These results suggest that the effect of fluoxetine on the expression of hSERT is post-translational and has shown itself to be independent of PKC and PKA activity.", "entity1": "PKC", "entity2": "fluoxetine", "span1": [143, 146], "span2": [41, 51]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4882": {"label": 3, "data": {"text": "5'-flanking region of glut3-luciferase reporter transient transfection in HT22 hippocampal neurons demonstrated that (m)CpGs inhibit glut3 transcription.", "entity1": "glut3", "entity2": "(m)CpGs", "span1": [133, 138], "span2": [117, 124]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7832": {"label": 2, "data": {"text": "Nevertheless, low L-BMAA concentrations (\u2265 0.1mM, 48 h) increased protein ubiquitination, 20S proteasomal and caspase 12 activity, expression of the endoplasmic reticulum (ER) stress marker CHOP, and enhanced phosphorylation of elf2\u03b1 in SH-SY5Y cells.", "entity1": "20S proteasomal", "entity2": "L-BMAA", "span1": [90, 105], "span2": [18, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15590": {"label": 1, "data": {"text": "IPI-926 is highly bound to plasma proteins and has minimal interaction with human \u03b1-1-acid glycoprotein.", "entity1": "human \u03b1-1-acid glycoprotein", "entity2": "IPI-926", "span1": [76, 103], "span2": [0, 7]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3139": {"label": 9, "data": {"text": "Amitriptyline, but not any other tricyclic or selective serotonin reuptake inhibitor antidepressants, promotes TrkA autophosphorylation in primary neurons and induces neurite outgrowth in PC12 cells.", "entity1": "TrkA", "entity2": "tricyclic", "span1": [111, 115], "span2": [33, 42]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"6232": {"label": 1, "data": {"text": "However, [3H]eletriptan had over 6-fold higher affinity than [3H]sumatriptan at the 5-HT1D receptor (K(D)): 0.92 and 6.58 nM, respectively) and over 3-fold higher affinity than [3H]sumatriptan at the 5-HT1B receptor (K(D): 3.14 and 11.07 nM, respectively).", "entity1": "5-HT1B", "entity2": "[3H]eletriptan", "span1": [200, 206], "span2": [9, 23]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3693": {"label": 3, "data": {"text": "Insulin secretion stimulated by both 200 \u03bcM tolbutamide and 20 \u03bcM gliclazide, concentrations that had equivalent effects on membrane potential, was inhibited by thapsigargin (1 \u03bcM) or the L-type Ca(2+) channel blocker nicardipine (2 \u03bcM) and was potentiated by 8-pCPT-2'-O-Me-cAMP-AM at concentrations \u22652 \u03bcM in INS-1 cells.", "entity1": "Insulin", "entity2": "nicardipine", "span1": [0, 7], "span2": [218, 229]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9509": {"label": 1, "data": {"text": "In conclusion, these findings indicate that [3H]SR 142948A is a new potent antagonist radioligand which recognizes with high affinity both neurotensin NT1 and NT2 receptors and represents thus an excellent tool to study neurotensin receptors in the rat brain.", "entity1": "neurotensin receptors", "entity2": "[3H]SR 142948A", "span1": [220, 241], "span2": [44, 58]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11868": {"label": 1, "data": {"text": "We examined the effects of anthocyanidins (cyanidin, delphinidin, malvidin, peonidin, petunidin, pelargonidin) on the aryl hydrocarbon receptor (AhR)-CYP1A1 signaling pathway in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cells.", "entity1": "CYP1A1", "entity2": "malvidin", "span1": [150, 156], "span2": [66, 74]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10730": {"label": 4, "data": {"text": "Binding domains of the oxytocin receptor for the selective oxytocin receptor antagonist barusiban in comparison to the agonists oxytocin and carbetocin.", "entity1": "oxytocin receptor", "entity2": "carbetocin", "span1": [59, 76], "span2": [141, 151]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11423": {"label": 8, "data": {"text": "Then the cells were treated with various concentrations of apoE3, lactoferrin and bovine serum albumin with or without 100 microg/ml of GMC, and the SGLT1-dependent methyl alpha-D-glucopyranoside (AMG) uptake and levels of SGLT1 expression were determined.", "entity1": "SGLT1", "entity2": "AMG", "span1": [149, 154], "span2": [197, 200]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15752": {"label": 2, "data": {"text": "Thus, CYP2E1-mediated ethanol hepatotoxicity was alleviated by quercetin through HO-1 induction.", "entity1": "HO-1", "entity2": "quercetin", "span1": [81, 85], "span2": [63, 72]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9295": {"label": 9, "data": {"text": "We conclude that expression of GLUT2 is required for efficient killing of neuroendocrine cells by STZ, and this effect is related to specific recognition of the drug as a transported substrate by GLUT2 but not GLUT1.", "entity1": "GLUT1", "entity2": "STZ", "span1": [210, 215], "span2": [98, 101]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, 8, -1, -1, -1, 9]},
	"4522": {"label": 8, "data": {"text": "Carboxylesterases hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively.", "entity1": "Carboxylesterases", "entity2": "esters", "span1": [0, 17], "span2": [28, 34]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"336": {"label": 3, "data": {"text": "The refolding kinetics of guanidine-denatured disulfide-intact bovine pancreatic ribonuclease A (RNase A) and its proline-42-to-alanine mutant (Pro42Ala) have been studied by monitoring tyrosine burial and 2'-cytidine monophosphate (2'CMP) inhibitor binding.", "entity1": "Pro42Ala", "entity2": "2'CMP", "span1": [144, 152], "span2": [233, 238]}, "weak_labels": [-1, -1, 0, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9605": {"label": 9, "data": {"text": "Mutation in the Walker A and B motifs of NBF2 of SUR1 abolished this stabilizing effect of MgADP.", "entity1": "NBF2", "entity2": "MgADP", "span1": [41, 45], "span2": [91, 96]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13455": {"label": 2, "data": {"text": "We demonstrate that only treatment of HaCaT with GLA and EPA or a PPARgamma ligand (roziglitazone), induced COX-2 expression (protein and mRNA).", "entity1": "COX-2", "entity2": "GLA", "span1": [108, 113], "span2": [49, 52]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7135": {"label": 1, "data": {"text": "All PDE5 constructs had similar affinities for 3-isobutyl-1-methylxanthine, sildenafil, tadalafil, and UK-122764, but mutants containing a complete GAF-B had 7- to 18-fold higher affinity for vardenafil-based compounds compared with those lacking a complete GAF-B.", "entity1": "PDE5", "entity2": "tadalafil", "span1": [4, 8], "span2": [88, 97]}, "weak_labels": [-1, -1, 0, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"244": {"label": 1, "data": {"text": "The isomers of MDA produced a concentration dependent increase in phosphatidyl inositol (PI) hydrolysis at the 5-HT2A receptors, with the R(-) isomer of MDA being more potent than the S(+) at the 5-HT2A receptor.", "entity1": "5-HT2A", "entity2": "R(-) isomer of MDA", "span1": [196, 202], "span2": [138, 156]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"12716": {"label": 1, "data": {"text": "These findings demonstrate that the addition of spacer linkages to bivalent yohimbine molecules provides a successful approach to the development of ligands that are potent and highly selective for the alpha2C-adrenoceptor.", "entity1": "alpha2C-adrenoceptor", "entity2": "yohimbine", "span1": [202, 222], "span2": [76, 85]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9560": {"label": 2, "data": {"text": "The observed inhibition on IFN-gamma, GM-CSF, and IL-3 mRNA was blocked by the selective beta2AR antagonist ICI 118,551 (10(-6) M) and by timolol (10(-6) M), a nonselective antagonist.", "entity1": "GM-CSF", "entity2": "ICI 118,551", "span1": [38, 44], "span2": [108, 119]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5081": {"label": 3, "data": {"text": "FCEO significantly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) by suppressing the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, respectively.", "entity1": "inducible nitric oxide synthase", "entity2": "nitric oxide", "span1": [116, 147], "span2": [29, 41]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8781": {"label": 3, "data": {"text": "Treatment with CAPE decreased protein abundance of Akt, Akt1, Akt2, Akt3, phospho-Akt Ser473, phospho-Akt Thr 308, GSK3\u03b2, FOXO1, FOXO3a, phospho-FOXO1 Thr24, phospho-FoxO3a Thr32, NF-\u03baB, phospho-NF-\u03baB Ser536, Rb, phospho-Rb Ser807/811, Skp2, and cyclin D1, but increased cell cycle inhibitor p27Kip.", "entity1": "Akt3", "entity2": "CAPE", "span1": [68, 72], "span2": [15, 19]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15408": {"label": 1, "data": {"text": "This study evaluates the production of inflammatory biomarkers (IL-1\u03b2, IL-8, IL-10, TNF\u03b1) and the influence of gene expression transporters and enzymes related to cholesterol absorption and metabolism (NPC1L1, ABCG5/8, HMGCoA, ACAT) produced by 7-ketosterols (stigmasterol/cholesterol) in Caco-2 cells.", "entity1": "IL-8", "entity2": "stigmasterol", "span1": [71, 75], "span2": [260, 272]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 8, -1, -1]},
	"15696": {"label": 1, "data": {"text": "Conclusion The results of this work contribute information regarding the antinociceptive properties of CAT on acute pain and show that, at least in part, TRPV1, TRPM8, ASIC, glutamate receptors, PKC and PKA participate in CAT's antinociceptive mechanism.", "entity1": "PKA", "entity2": "CAT", "span1": [203, 206], "span2": [222, 225]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5219": {"label": 2, "data": {"text": "Also, vinblastine enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaB\u03b1 (I\u03baB\u03b1) kinase, and inositol requiring enzyme 1\u03b1.", "entity1": "Ras homologous protein A", "entity2": "vinblastine", "span1": [50, 74], "span2": [6, 17]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3211": {"label": 3, "data": {"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1).", "entity1": "carbonic anhydrase", "entity2": "phenolic acids", "span1": [262, 280], "span2": [12, 26]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"10135": {"label": 3, "data": {"text": "Accordingly, docking of different COX inhibitors, including selective and non-selective ligands: rofecoxib, ketoprofen, suprofen, carprofen, zomepirac, indomethacin, diclofenac and meclofenamic acid were undertaken using the AMBER program.", "entity1": "COX", "entity2": "diclofenac", "span1": [34, 37], "span2": [166, 176]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3072": {"label": 3, "data": {"text": "PURPOSE: To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).", "entity1": "GABA transaminase", "entity2": "vigabatrin", "span1": [311, 328], "span2": [232, 242]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"16015": {"label": 5, "data": {"text": "The involvement of the various DA receptor subtypes in the motor effects of N/OFQ and NOP receptor antagonists was evaluated pharmacologically, using D1/D5 (SCH23390), D2/D3 (raclopride, amisulpride) and D3 (S33084) receptor antagonists, and by using D2 receptor knockout mice.", "entity1": "D2", "entity2": "raclopride", "span1": [168, 170], "span2": [175, 185]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8562": {"label": 8, "data": {"text": "Both types of granules contain catechol oxidase that catalyzes oxidative cross-linking of L-DOPA.", "entity1": "catechol oxidase", "entity2": "L-DOPA", "span1": [31, 47], "span2": [90, 96]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"2368": {"label": 3, "data": {"text": "Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.", "entity1": "RAF", "entity2": "BAY 43-9006", "span1": [71, 74], "span2": [11, 22]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14272": {"label": 8, "data": {"text": "We recently showed that TETA is metabolized in vitro by polyamine catabolic enzyme spermidine/spermine-N(1)-acetyltransferase (SSAT1) and by thialysine acetyltransferase (SSAT2) to its monoacetylated derivative (MAT).", "entity1": "SSAT1", "entity2": "TETA", "span1": [127, 132], "span2": [24, 28]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2622": {"label": 3, "data": {"text": "The activity of polymerases containing mutations known to confer resistance to foscarnet (V715M, T700A and N495K) was inhibited by concentrations of foscarnet eight to 14 times higher than those required to inhibit wild-type polymerases.", "entity1": "polymerases", "entity2": "foscarnet", "span1": [225, 236], "span2": [149, 158]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14157": {"label": 4, "data": {"text": "The mianserin analogue mirtazapine also displayed kappa-opioid agonist activity.", "entity1": "kappa-opioid", "entity2": "mianserin", "span1": [50, 62], "span2": [4, 13]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"882": {"label": 5, "data": {"text": "In the present study, we compared the pharmacology of (+/-)pindolol, WAY-100635 (a 5-HT(1A) antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and isamoltane (a 5-HT(1B) antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat.", "entity1": "5-HT(1B)", "entity2": "isamoltane", "span1": [160, 168], "span2": [146, 156]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5386": {"label": 2, "data": {"text": "In both OFC and mPFC, no strain differences in Vmax or Km for dopamine uptake into synaptosomes were found between vehicle-treated SHR, WKY and WIS. Methylphenidate increased DAT Vmax in SHR mPFC and decreased DAT Vmax in WKY OFC.", "entity1": "DAT", "entity2": "Methylphenidate", "span1": [175, 178], "span2": [149, 164]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8881": {"label": 2, "data": {"text": "TCDD induces the expression of insulin-like growth factor binding protein 4 in 5L rat hepatoma cells: a cautionary tale of the use of this cell line in studies on dioxin toxicity.", "entity1": "insulin-like growth factor binding protein 4", "entity2": "TCDD", "span1": [31, 75], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14154": {"label": 3, "data": {"text": "When combined, mianserin antagonized the effects of the full kappa-opioid receptor agonists in [(35)S]GTPgammaS assays and reduced the stimulation of p38 MAPK and ERK1/2 phosphorylation by dynorphin A.", "entity1": "MAPK", "entity2": "mianserin", "span1": [154, 158], "span2": [15, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, 3, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4019": {"label": 3, "data": {"text": "Compared with the untreated colitis group, the curcumin-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-\u03baB mRNA, IL-27 mRNA, TLR4 protein, NF-\u03baB p65 protein, and IL-27 p28 protein (p < 0.05).", "entity1": "myeloperoxidase", "entity2": "curcumin", "span1": [179, 194], "span2": [47, 55]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3044": {"label": 8, "data": {"text": "PGE(2) is synthesized from arachidonic acid by cyclooxygenases (COX) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4).", "entity1": "COX", "entity2": "PGE(2)", "span1": [64, 67], "span2": [0, 6]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6982": {"label": 1, "data": {"text": "Bisoprolol markedly suppressed the dobutamine-induced PRA increase in Arg389- but only marginally in Gly389-beta1AR subjects.", "entity1": "beta1AR", "entity2": "dobutamine", "span1": [108, 115], "span2": [35, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14315": {"label": 1, "data": {"text": "However, downregulation of the antioxidant response element (ARE)-driven Nrf2 target genes such as NQO1, HO-1 and glutathione S-transferase (GST) did not reverse the inhibitory effect of DMF on TGF-beta-induced upregulation of profibrotic genes or extracellular matrix proteins, suggesting an ARE-independent anti-fibrotic activity of DMF.", "entity1": "antioxidant response element", "entity2": "DMF", "span1": [31, 59], "span2": [187, 190]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, 2, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"15875": {"label": 3, "data": {"text": "In K(+)-depolarized tissues, D3 receptors potentiated D1 receptor-induced stimulation of [(3)H]GABA release only when CaMKII\u03b1 was blocked with KN-62.", "entity1": "CaMKII\u03b1", "entity2": "KN-62", "span1": [118, 125], "span2": [143, 148]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11447": {"label": 1, "data": {"text": "DAT occupancy was determined by displacement of 8-(2-[(18)F]fluroethyl)2beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane (FECNT).", "entity1": "DAT", "entity2": "FECNT", "span1": [0, 3], "span2": [124, 129]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13877": {"label": 2, "data": {"text": "In addition, another study suggests that ibuprofen reduces generation of amyloid-beta42 peptide via inactivation of RhoA signaling, although it may also regulate amyloid-beta42 formation by direct inhibition of the gamma-secretase complex.", "entity1": "amyloid-beta42", "entity2": "ibuprofen", "span1": [162, 176], "span2": [41, 50]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7984": {"label": 2, "data": {"text": "These results demonstrated for the first time that ISO induces apoptosis in HepG2 cells through inactivating ERK1/2 kinase and activating JNK and p38 kinases, and ROS stimulated by ISO is able to activate the MAPK singaling pathway as the upstream signaling molecules.", "entity1": "JNK", "entity2": "ISO", "span1": [138, 141], "span2": [51, 54]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7891": {"label": 1, "data": {"text": "Data suggest that bisphosphonates via modulation of the activity of small-GTPases induce apoptosis in neoplastic cells by DNA-CpG-demethylation and stimulation of FAS-expression.", "entity1": "GTPases", "entity2": "bisphosphonates", "span1": [74, 81], "span2": [18, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13805": {"label": 3, "data": {"text": "The most successful example of kinase blockers is Imatinib (Imatinib mesylate, Gleevec, STI571), the inhibitor of Bcr/Abl oncoprotein, which has become a first-line therapy for chronic myelogenous leukemia.", "entity1": "Bcr", "entity2": "STI571", "span1": [114, 117], "span2": [88, 94]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5718": {"label": 1, "data": {"text": "The AKR1C3\u00b7NADP(+)\u00b72'-des-methyl-indomethacin crystal structure was determined, and it revealed a unique inhibitor binding mode.", "entity1": "AKR1C3", "entity2": "2'-des-methyl-indomethacin", "span1": [4, 10], "span2": [19, 45]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10813": {"label": 3, "data": {"text": "As expected, comparison of IC50 indicated that meloxicam and carprofen are more selective inhibitors of COX-2 than phenylbutazone and flunixin; meloxicam was the most advantageous for horses of four NSAIDs examined.", "entity1": "COX-2", "entity2": "phenylbutazone", "span1": [104, 109], "span2": [115, 129]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6022": {"label": 3, "data": {"text": "Indomethacin, piroxicam, and sulindac sulfide were found to preferentially inhibit PGHS-1.", "entity1": "PGHS-1", "entity2": "sulindac sulfide", "span1": [83, 89], "span2": [29, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13043": {"label": 8, "data": {"text": "Here we demonstrate that PPARgamma, turns on retinoic acid synthesis by inducing the expression of retinol and retinal metabolizing enzymes such as retinol dehydrogenase 10 and retinaldehyde dehydrogenase type 2 (RALDH2).", "entity1": "retinaldehyde dehydrogenase type 2", "entity2": "retinoic acid", "span1": [177, 211], "span2": [45, 58]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6063": {"label": 3, "data": {"text": "The mechanism by which norepinephrine (NE) down-regulates alpha 1B-adrenergic receptor (alpha-AR) mRNA was studied in rabbit aortic smooth muscle cells.", "entity1": "alpha 1B-adrenergic receptor", "entity2": "norepinephrine", "span1": [58, 86], "span2": [23, 37]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13674": {"label": 0, "data": {"text": "Both porcine TLR7 and TLR8 proteins were expressed in cell lines and were N-glycosylated.", "entity1": "porcine TLR7", "entity2": "N", "span1": [5, 17], "span2": [74, 75]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11056": {"label": 9, "data": {"text": "Activation of Atp8a1 is also reduced by these modifications; phosphatidylserine-O-methyl ester, lysophosphatidylserine, glycerophosphoserine, and phosphoserine, which are not transported by the plasma membrane flippase, do not activate Atp8a1.", "entity1": "Atp8a1", "entity2": "lysophosphatidylserine", "span1": [236, 242], "span2": [96, 118]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, 9]},
	"11001": {"label": 1, "data": {"text": "Interestingly, exposure to a lower concentration (1 microM) of the antidepressants tended to increase T-cell-derived IL-10 production, with significant effects elicited by the noradrenaline reuptake inhibitors reboxetine and desipramine.", "entity1": "IL-10", "entity2": "desipramine", "span1": [117, 122], "span2": [225, 236]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"2602": {"label": 0, "data": {"text": "In addition to the N-terminal and Src homology 2 domains that mediate these interactions, SOCS proteins contain a C-terminal SOCS box.", "entity1": "Src homology 2 domains", "entity2": "N", "span1": [34, 56], "span2": [19, 20]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1531": {"label": 8, "data": {"text": "The beta subunit has been cloned and shown to lower the K(m) of methionine adenosyltransferase II alpha2 (the MAT2A product) for methionine and to render the enzyme more susceptible to S-adenosylmethionine inhibition.", "entity1": "methionine adenosyltransferase II alpha2", "entity2": "methionine", "span1": [64, 104], "span2": [129, 139]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"13372": {"label": 2, "data": {"text": "Estrogen-regulated genes including cytokeratin 1-19 and Cyp2a4 were over-expressed, although Cyp3a25 was suppressed.", "entity1": "cytokeratin 1-19", "entity2": "Estrogen", "span1": [35, 51], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15022": {"label": 3, "data": {"text": "In agreement with these data, the exogenous treatment of SAH or inhibition of SAHH by specific siRNA or another type of inhibitor, 3-deazaadenosine (DAZA), similarly resulted in antitumorigenic responses, suppressive activity on Src, the alteration of actin cytoskeleton, and a change of the colocalization pattern between actin and Src.", "entity1": "SAHH", "entity2": "3-deazaadenosine", "span1": [78, 82], "span2": [131, 147]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"5099": {"label": 1, "data": {"text": "In addition, 5HHMF blocked LPS-induced phosphorylation of I\u03baB, resulting in suppression of the nuclear translocation of nuclear factor-\u03baB (NF-\u03baB) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression.", "entity1": "iNOS", "entity2": "5HHMF", "span1": [236, 240], "span2": [13, 18]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9960": {"label": 3, "data": {"text": "Selective COX-2 inhibitors, such as meloxicam, celecoxib (SC-58635), and rofecoxib (MK-0966), are NSAIDs that have been modified chemically to preferentially inhibit COX-2 but not COX-1.", "entity1": "COX-2", "entity2": "meloxicam", "span1": [10, 15], "span2": [36, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"10107": {"label": 8, "data": {"text": "The elevation in brain alanine levels could be explained, at least in part, by a time- and dose-dependent inhibitory effect of PLZ on alanine transaminase (ALA-T), although as with GABA the increases are higher than expected from the degree of enzyme inhibition produced.", "entity1": "alanine transaminase", "entity2": "alanine", "span1": [134, 154], "span2": [23, 30]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"2102": {"label": 4, "data": {"text": "The selective betaAR agonist isoproterenol caused an enhancement of hippocampal CA3 network activity, as measured by an increase in frequency of spontaneous burst discharges recorded in the CA3 region.", "entity1": "betaAR", "entity2": "isoproterenol", "span1": [14, 20], "span2": [29, 42]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11143": {"label": 3, "data": {"text": "We have examined the effect of dihydropyridine Ca2+-channel blockers felodipine and nicardipine on CaMPDE.", "entity1": "Ca2+-channel", "entity2": "felodipine", "span1": [47, 59], "span2": [69, 79]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11422": {"label": 8, "data": {"text": "Then the cells were treated with various concentrations of apoE3, lactoferrin and bovine serum albumin with or without 100 microg/ml of GMC, and the SGLT1-dependent methyl alpha-D-glucopyranoside (AMG) uptake and levels of SGLT1 expression were determined.", "entity1": "SGLT1", "entity2": "methyl alpha-D-glucopyranoside", "span1": [149, 154], "span2": [165, 195]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"17": {"label": 3, "data": {"text": "Preincubation for 30 minutes with iloprost, ciprostene, and carbacyclin led to a dose-dependent inhibition of tissue factor expression induced by all three challenging agents.", "entity1": "tissue factor", "entity2": "iloprost", "span1": [110, 123], "span2": [34, 42]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2975": {"label": 1, "data": {"text": "Change in affinity for cGMP, vardenafil, sildenafil, or IBMX in Y612F, H613A, L765A, or F786A was less, but affinity of H613A or F786A for tadalafil was weakened 37- and 17-fold, respectively.", "entity1": "H613A", "entity2": "IBMX", "span1": [71, 76], "span2": [56, 60]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4044": {"label": 3, "data": {"text": "The molecular mechanism studies suggested that neoechinulin A may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-\u03baB (NF-\u03baB) p65 and p50 subunits.", "entity1": "nuclear factor-\u03baB", "entity2": "neoechinulin A", "span1": [223, 240], "span2": [47, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"789": {"label": 1, "data": {"text": "Analysis of splice variants and site-directed mutants of the AMPAAMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the GluR3 flop splice variant and suggested that lithium might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function.", "entity1": "AMPA receptor", "entity2": "AMPA", "span1": [65, 78], "span2": [61, 65]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"5858": {"label": 5, "data": {"text": "A number of selective 5-HT3 antagonists have been developed including ondansetron, granisetron, tropisetron renzapride and zacopride.", "entity1": "5-HT3", "entity2": "granisetron", "span1": [22, 27], "span2": [83, 94]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15152": {"label": 1, "data": {"text": "Expression of pituitary FSH and LH, under the control of pulsatile GnRH, is essential for fertility.", "entity1": "FSH", "entity2": "GnRH", "span1": [24, 27], "span2": [67, 71]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11848": {"label": 1, "data": {"text": "We conclude that there are prejunctional A1Rs in arteries and both pre- and postjunctional A1Rs in veins; thus, adenosine selectively constricts the veins.", "entity1": "A1Rs", "entity2": "adenosine", "span1": [91, 95], "span2": [112, 121]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13507": {"label": 6, "data": {"text": "These data indicate that vecuronium, gallamine and pancuronium interact with an allosteric site on the muscarinic M2 receptor (located on the heart) and this may explain some of their cardiac side effects.", "entity1": "muscarinic M2 receptor", "entity2": "pancuronium", "span1": [103, 125], "span2": [51, 62]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1]},
	"3701": {"label": 2, "data": {"text": "In addition, the number and area of glutathione S-transferase placental form (GST-P) positive foci and proliferating cell nuclear antigen (PCNA) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg/kg MEG compared with the control animals.", "entity1": "glutathione S-transferase placental form", "entity2": "MEG", "span1": [36, 76], "span2": [274, 277]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4761": {"label": 3, "data": {"text": "Previously, we have found that BRN-103, a nicotinamide derivative, inhibits vascular endothelial growth factor (VEGF)-mediated angiogenesis signaling in human endothelial cells.", "entity1": "vascular endothelial growth factor", "entity2": "BRN-103", "span1": [76, 110], "span2": [31, 38]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15028": {"label": 8, "data": {"text": "Treatment with adenosine dialdehyde (AdOx), an inhibitor of transmethylation-suppressive adenosylhomocysteine (SAH) hydrolase (SAHH), enhanced the level of SAH and effectively blocked the proliferation, migration, and invasion of cancer cells; the treatment also induced the differentiation of C6 glioma cells and suppressed the neovascular genesis of eggs in a dose-dependent manner.", "entity1": "adenosylhomocysteine (SAH) hydrolase", "entity2": "SAH", "span1": [89, 125], "span2": [156, 159]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7137": {"label": 1, "data": {"text": "All PDE5 constructs had similar affinities for 3-isobutyl-1-methylxanthine, sildenafil, tadalafil, and UK-122764, but mutants containing a complete GAF-B had 7- to 18-fold higher affinity for vardenafil-based compounds compared with those lacking a complete GAF-B.", "entity1": "PDE5", "entity2": "UK-122764", "span1": [4, 8], "span2": [103, 112]}, "weak_labels": [-1, -1, 0, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14943": {"label": 2, "data": {"text": "Peginesatide, a polyethylene glycol (PEG)ylated peptide-based erythropoiesis-stimulating agent, stimulates the erythropoietin receptor dimer that governs erythropoiesis.", "entity1": "erythropoietin receptor", "entity2": "PEG", "span1": [111, 134], "span2": [37, 40]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12281": {"label": 3, "data": {"text": "This study identified four clinically approved antihypertensive drugs (efonidipine, felodipine, isradipine, and nitrendipine) as potent T-channel blockers (IC(50) < 3 microM).", "entity1": "T-channel", "entity2": "nitrendipine", "span1": [136, 145], "span2": [112, 124]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9879": {"label": 5, "data": {"text": "We examined the effect of JTH-601 (3- inverted question markN-[2-(4-hydroxy-2-isopropyl-5-methylphenoxy)ethyl]-N-methylaminom ethyl inverted question mark-4-methoxy-2,5,6-trimethylphenol hemifumarate), a new alpha(1L)-adrenoceptor antagonist, on prostatic function in isolated canine prostate and in anesthetized dogs.", "entity1": "alpha(1L)-adrenoceptor", "entity2": "N-[2-(4-hydroxy-2-isopropyl-5-methylphenoxy)ethyl]-N-methylaminom", "span1": [208, 230], "span2": [60, 125]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"16043": {"label": 3, "data": {"text": "Rats intoxicated with Cd for 30 days, significantly increased tissue malondialdehyde (MDA) levels and significantly decreased enzymatic antioxidants superoxide dismutase, glutathione peroxidase and catalase in the frontal cortex tissue.", "entity1": "catalase", "entity2": "Cd", "span1": [198, 206], "span2": [22, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2104": {"label": 5, "data": {"text": "In contrast, the selective beta2AR antagonists ICI-118,551 and butoxamine inhibited isoproterenol-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively).", "entity1": "beta2AR", "entity2": "butoxamine", "span1": [27, 34], "span2": [63, 73]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9965": {"label": 3, "data": {"text": "Selective COX-2 inhibitors, such as meloxicam, celecoxib (SC-58635), and rofecoxib (MK-0966), are NSAIDs that have been modified chemically to preferentially inhibit COX-2 but not COX-1.", "entity1": "COX-2", "entity2": "rofecoxib", "span1": [166, 171], "span2": [73, 82]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"5827": {"label": 3, "data": {"text": "In summary, loperamide is able to reduce basal and CRH-induced ACTH and cortisol levels in normal subjects, but not in patients with Cushing's disease or secondary adrenal failure of hypothalamic origin.", "entity1": "ACTH", "entity2": "loperamide", "span1": [63, 67], "span2": [12, 22]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"12105": {"label": 3, "data": {"text": "HERG/IKr channels are a prime target for the pharmacological management of arrhythmias and are selectively blocked by class III antiarrhythmic methanesulfonanilide drugs, such as dofetilide, E4031, and MK-499, at submicromolar concentrations.", "entity1": "HERG", "entity2": "MK-499", "span1": [0, 4], "span2": [202, 208]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"79": {"label": 3, "data": {"text": "Although the precise mechanism of the protective action of trilisate is unknown, our data support the possibility of interaction between salicylate and ASA on cyclo-oxygenase locus in the respiratory tract in ASA-intolerant patients.", "entity1": "cyclo-oxygenase", "entity2": "salicylate", "span1": [159, 174], "span2": [137, 147]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14503": {"label": 3, "data": {"text": "Western blot analysis indicated that TSN inhibits the CDC42/MEKK1/JNK pathway.", "entity1": "JNK", "entity2": "TSN", "span1": [66, 69], "span2": [37, 40]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6304": {"label": 5, "data": {"text": "These responses were effectively blocked by the 5-HT1B receptor antagonist, isamoltane, the 5-HT1B/5-HT2 receptor antagonist, methiothepin, and the eNOS selective antagonists (0.01-10 microM): L-Nomega -monomethyl-L-arginine (L-NMMA) and L-N omega-iminoethyl-L-ornithine (L-NIO).", "entity1": "5-HT2 receptor", "entity2": "methiothepin", "span1": [99, 113], "span2": [126, 138]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5224": {"label": 2, "data": {"text": "Also, vinblastine enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaB\u03b1 (I\u03baB\u03b1) kinase, and inositol requiring enzyme 1\u03b1.", "entity1": "I\u03baB\u03b1", "entity2": "vinblastine", "span1": [277, 281], "span2": [6, 17]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1723": {"label": 3, "data": {"text": "The inhibitory effect of ginseng saponins on the stress-induced plasma interleukin-6 level in mice.", "entity1": "interleukin-6", "entity2": "ginseng saponins", "span1": [71, 84], "span2": [25, 41]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"706": {"label": 3, "data": {"text": "The acute toxicity of organophosphorus (OP) compounds in mammals is due to their irreversible inhibition of acetylcholinesterase (AChE) in the nervous system, which leads to increased synaptic acetylcholine levels.", "entity1": "acetylcholinesterase", "entity2": "organophosphorus", "span1": [108, 128], "span2": [22, 38]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"274": {"label": 3, "data": {"text": "The channel activators avermectin and moxidectin usually retain their inhibitory potency in the Rdl subunit mutants.", "entity1": "Rdl", "entity2": "moxidectin", "span1": [96, 99], "span2": [38, 48]}, "weak_labels": [-1, -1, 0, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10274": {"label": 8, "data": {"text": "The outflow of [3H]-MPP+ was significantly enhanced by MPP+, guanidine, choline and amantadine as potential substrates for OCT-related transmembrane transporters.", "entity1": "OCT", "entity2": "choline", "span1": [123, 126], "span2": [72, 79]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, 8, -1, -1, -1, -1]},
	"14514": {"label": 1, "data": {"text": "Filtering and analysis of data identified three oncogenic pathways interfered by 5-ASA: MAPK/ERK pathway, cell adhesion and \u03b2-catenin/Wnt signaling.", "entity1": "MAPK", "entity2": "5-ASA", "span1": [88, 92], "span2": [81, 86]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10567": {"label": 1, "data": {"text": "To verify the hypothesis that the non-conventional partial agonist (-)-CGP12177 binds at two beta(1)-adrenoceptor sites, human beta(1)-adrenoceptors, expressed in CHO cells, were labelled with (-)-[(3)H]-CGP12177.", "entity1": "human beta(1)-adrenoceptors", "entity2": "(-)-CGP12177", "span1": [121, 148], "span2": [67, 79]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7004": {"label": 3, "data": {"text": "Significant advances in the treatment of clear-cell RCC have been derived from agents that target these pathways, including the multiple-kinase inhibitors (MKIs) sorafenib, sunitinib, and AG013736, which target multiple VEGFRs as well as PDGFR-beta.", "entity1": "VEGFRs", "entity2": "sorafenib", "span1": [220, 226], "span2": [162, 171]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1432": {"label": 3, "data": {"text": "They included the COX-1 inhibitor indomethacin; the COX-2 inhibitor NS-398; the mixed COX-1/COX-2 inhibitor ibuprofen; the nitric oxide (NO) derivatives of indomethacin, ibuprofen and flurbiprofen; the 5-LOX inhibitor REV 5901; and the 5-LOX activating protein (FLAP) inhibitor MK-886.", "entity1": "COX-1", "entity2": "ibuprofen", "span1": [86, 91], "span2": [108, 117]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4641": {"label": 2, "data": {"text": "Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent activator of AhR.", "entity1": "CYP1A1", "entity2": "2,3,7,8-tetrachlorodibenzodioxin", "span1": [50, 56], "span2": [135, 167]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13031": {"label": 2, "data": {"text": "Mutations in the 11beta-HSD2 gene cause a rare form of inherited hypertension, the syndrome of apparent mineralocorticoid excess (AME), in which cortisol activates the MR resulting in severe hypertension and hypokalemia.", "entity1": "MR", "entity2": "cortisol", "span1": [168, 170], "span2": [145, 153]}, "weak_labels": [-1, -1, 0, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2516": {"label": 3, "data": {"text": "Our results demonstrated that auranofin suppressed TLR4-mediated activation of transcription factors, NF-kappaB and IRF3, and expression of COX-2, a pro-inflammatory enzyme.", "entity1": "TLR4", "entity2": "auranofin", "span1": [51, 55], "span2": [30, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8676": {"label": 2, "data": {"text": "The expression kinetics of TAp63, c-Abl and TAp73 suggest that cisplatin activates TAp63-dependent expression of c-Abl and TAp73 and, in turn, the activation of TAp73 by c-Abl-induced BAX expression.", "entity1": "TAp73", "entity2": "cisplatin", "span1": [123, 128], "span2": [63, 72]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14692": {"label": 3, "data": {"text": "This study provides a mechanistic understanding of the in vivo inhibition of transporters and enzymes by GSK1292263.", "entity1": "transporters", "entity2": "GSK1292263", "span1": [77, 89], "span2": [105, 115]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"13249": {"label": 5, "data": {"text": "The GRIP1 reduction was inhibited by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an AMPA receptor antagonist.", "entity1": "AMPA receptor", "entity2": "CNQX", "span1": [156, 169], "span2": [146, 150]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3351": {"label": 1, "data": {"text": "The structural and functional data reveal that the levosimendan class of Ca(2+)-sensitizers work by binding to the regulatory domain of cTnC and stabilizing the pivotal cTnC-cTnI regulatory unit via a network of hydrophobic and electrostatic interactions, in contrast to the destabilizing effects of antagonists such as W7 at the same interface.", "entity1": "cTnC", "entity2": "levosimendan", "span1": [136, 140], "span2": [51, 63]}, "weak_labels": [-1, -1, -1, 1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11624": {"label": 1, "data": {"text": "The immunosuppressive effects of T3 SCI were caused by NE acting at beta2-adrenergic receptors (beta2AR) and could be reversed using beta2AR blockers.", "entity1": "beta2-adrenergic receptors", "entity2": "NE", "span1": [68, 94], "span2": [55, 57]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13419": {"label": 8, "data": {"text": "Furthermore, the enzymatic activity of alanine aminotransferase (ALT), which converts the critical gluconeogenic amino acid alanine into pyruvate, is decreased (approximately 50%) in KLF15-/- hepatocytes.", "entity1": "alanine aminotransferase", "entity2": "amino acid", "span1": [39, 63], "span2": [113, 123]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, 9]},
	"1785": {"label": 1, "data": {"text": "Tamsulosin, which has high affinity for alpha1aAR and alpha1dAR subtypes but not for alpha1bAR, shows efficacy similar to the nonsubtype selective agents terazosin and doxazosin.", "entity1": "alpha1aAR", "entity2": "terazosin", "span1": [40, 49], "span2": [154, 163]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"6998": {"label": 8, "data": {"text": "Involvement of COX-1 and up-regulated prostaglandin E synthases in phosphatidylserine liposome-induced prostaglandin E2 production by microglia.", "entity1": "COX-1", "entity2": "prostaglandin E2", "span1": [15, 20], "span2": [103, 119]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"2166": {"label": 3, "data": {"text": "In vitro inhibitory effects of non-steroidal anti-inflammatory drugs on 4-methylumbelliferone glucuronidation in recombinant human UDP-glucuronosyltransferase 1A9--potent inhibition by niflumic acid.", "entity1": "human UDP-glucuronosyltransferase 1A9", "entity2": "niflumic acid", "span1": [125, 162], "span2": [185, 198]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1555": {"label": 2, "data": {"text": "Treatment with diclofenac resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated caspase-3 after 6 hr, indicating that diclofenac may cause apoptosis of neuronal cells via activation of the caspase cascade.", "entity1": "caspase", "entity2": "diclofenac", "span1": [257, 264], "span2": [186, 196]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11553": {"label": 1, "data": {"text": "Occupancy of dopamine D(1), D (2) and serotonin (2A) receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol.", "entity1": "serotonin (2A) receptors", "entity2": "haloperidol", "span1": [38, 62], "span2": [149, 160]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3445": {"label": 5, "data": {"text": "These results confirm the selective mGlu2 agonist and mGlu3 antagonist actions of LY541850.", "entity1": "mGlu3", "entity2": "LY541850", "span1": [54, 59], "span2": [82, 90]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"353": {"label": 1, "data": {"text": "These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to clonidine and endogenous clonidine-displacing substance(s), and may serve as markers of imidazoline receptors in humans.", "entity1": "imidazoline receptors", "entity2": "clonidine", "span1": [205, 226], "span2": [142, 151]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15554": {"label": 2, "data": {"text": "Extrinsic apoptotic pathway markers such as Fas levels and caspase-8 activity increased as a result of CdTe-QD exposure.", "entity1": "Fas", "entity2": "CdTe", "span1": [44, 47], "span2": [103, 107]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4991": {"label": 1, "data": {"text": "Cobalt chloride, a typical HIF activator, induced the gene expression of CAR-target genes, including cyp2b9 and cyp2b10, an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver.", "entity1": "CAR", "entity2": "Cobalt chloride", "span1": [73, 76], "span2": [0, 15]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8896": {"label": 4, "data": {"text": "In the hot-plate test in mice, the antinociceptive action of the alpha 2-adrenoceptor agonist, UK 14,304, was abolished by the alpha 2-adrenoceptor antagonist, idazoxan, the potent alpha 2A-adrenoceptor antagonist, RX 821002 and the preferential alpha 2A-adrenoceptor antagonist, BRL 44408.", "entity1": "alpha 2-adrenoceptor", "entity2": "UK 14,304", "span1": [65, 85], "span2": [95, 104]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"741": {"label": 5, "data": {"text": "The beta-adrenergic/5-HT1A receptor antagonist (+/-)pindolol and the selective 5-HT1B/D antagonist GR127935 produced no significant augmentation of venlafaxine-induced changes in either 5-HT or NA.", "entity1": "5-HT1A", "entity2": "(+/-)pindolol", "span1": [20, 26], "span2": [47, 60]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"8920": {"label": 2, "data": {"text": "The vasopressor response to the calcium channel activator, BAY-K-8644, which is mediated through the opening of voltage dependent calcium channels and the subsequent translocation of extracellular calcium, was significantly inhibited by carvedilol (1 mg/kg, iv), suggesting that carvedilol is also a calcium channel antagonist, consistent with our previous in vitro studies.", "entity1": "voltage dependent calcium channels", "entity2": "BAY-K-8644", "span1": [112, 146], "span2": [59, 69]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13351": {"label": 1, "data": {"text": "In addition, BALB/c and C57BL/6 females were treated with progesterone or MPA for 1 or 2 months, and mammary glands were excised for histologic studies and for immunohistochemical and Western blot evaluation of ER and PR.", "entity1": "PR", "entity2": "MPA", "span1": [218, 220], "span2": [74, 77]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15671": {"label": 3, "data": {"text": "3-Hydroxypyridin-2-thione as Novel Zinc Binding Group for Selective Histone Deacetylase Inhibition.", "entity1": "Histone Deacetylase", "entity2": "Zinc", "span1": [68, 87], "span2": [35, 39]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5201": {"label": 3, "data": {"text": "Inhibition of mTOR by low dose rapamycin decreases HG-induced Nox4 and Nox1, NADPH oxidase activity and podocyte apoptosis.", "entity1": "mTOR", "entity2": "rapamycin", "span1": [14, 18], "span2": [31, 40]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"818": {"label": 2, "data": {"text": "It was concluded that PGE1 selectively reduces both N- and R-type Ca2+ currents by activating a G-protein probably through the EP3 receptor in paratracheal ganglion cells.", "entity1": "G-protein", "entity2": "PGE1", "span1": [96, 105], "span2": [22, 26]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12299": {"label": 1, "data": {"text": "Quercetin supplementation altered expression profiles of several lipid metabolism-related genes, including Fnta, Pon1, Pparg, Aldh1b1, Apoa4, Abcg5, Gpam, Acaca, Cd36, Fdft1, and Fasn, relative to those in HFD control mice.", "entity1": "Acaca", "entity2": "Quercetin", "span1": [155, 160], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1881": {"label": 4, "data": {"text": "At 10(-6)M in transcription assays, none of these compounds showed progestin agonist activity, whereas mifepristone and its monodemethylated metabolite manifested slight glucocorticoid agonist activity.", "entity1": "glucocorticoid", "entity2": "mifepristone", "span1": [170, 184], "span2": [103, 115]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8962": {"label": 1, "data": {"text": "Radioligand binding studies with the nonselective alpha 1-adrenoceptor antagonist radioligand 125I-BE2254 showed that 73-87% of the binding sites in rabbit aorta are CEC sensitive and they are predominantly low affinity sites both for WB4101 (pKd = 8.1) and for 5-methylurapidil (pKd = 7.1).", "entity1": "alpha 1-adrenoceptor", "entity2": "CEC", "span1": [50, 70], "span2": [166, 169]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1003": {"label": 0, "data": {"text": "Peptide sequences selected using MICA4 were rich in basic or hydroxyl-containing amino acids, and the surface of the GAD65 PLP-binding domain surrounding Lys358, which is known to be critical for MICA4 binding, was likewise rich in these amino acids.", "entity1": "GAD65 PLP-binding domain", "entity2": "amino acids", "span1": [117, 141], "span2": [238, 249]}, "weak_labels": [0, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2634": {"label": 8, "data": {"text": "They all expressed ASS, but not ornithine transcarbamylase (OTC), the enzyme that converts ornithine, the product of degradation of arginine with rhArg, to citrulline, which is converted back to arginine via ASS.", "entity1": "OTC", "entity2": "ornithine", "span1": [60, 63], "span2": [91, 100]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, 8, 9]},
	"12835": {"label": 3, "data": {"text": "To test the role of nicotinic receptors in the drugs' effects on [3H]-ACh release, mecamylamine (MEC) 100 microM was used to block such receptors.", "entity1": "nicotinic receptors", "entity2": "mecamylamine", "span1": [20, 39], "span2": [83, 95]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3269": {"label": 1, "data": {"text": "NMR chemical shift perturbations are consistent with the crystal structure and demonstrate that TFP binds to the target binding cleft of S100A4 in solution.", "entity1": "S100A4", "entity2": "TFP", "span1": [137, 143], "span2": [96, 99]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"59": {"label": 3, "data": {"text": "The results of clinical trials with enalkiren are encouraging, and suggest that renin inhibitors may be safe, useful therapeutic agents in the management of hypertension.", "entity1": "renin", "entity2": "enalkiren", "span1": [80, 85], "span2": [36, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5882": {"label": 1, "data": {"text": "At beta 1-adrenoceptors, the affinity of the compound RR-SR was about 3 times that of labetalol.5.", "entity1": "beta 1-adrenoceptors", "entity2": "labetalol", "span1": [3, 23], "span2": [86, 95]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2380": {"label": 3, "data": {"text": "Further characterization of sorafenib revealed that this molecule was a multikinase inhibitor that targeted the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-beta and Kit), which play key roles in tumor progression and angiogenesis.", "entity1": "platelet-derived growth factor receptor", "entity2": "sorafenib", "span1": [189, 228], "span2": [28, 37]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8437": {"label": 1, "data": {"text": "The endogenous steroid lithocholic acid (LCA) dilates cerebral arteries via BK channel activation, which requires recognition by a BK \u03b21 site that includes Thr169.", "entity1": "BK channel", "entity2": "LCA", "span1": [76, 86], "span2": [41, 44]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3860": {"label": 3, "data": {"text": "HSYA suppressed the expression of TLR-4, Myd88, ICAM-1, TNF\u03b1, IL-1\u03b2 and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.", "entity1": "ICAM-1", "entity2": "HSYA", "span1": [48, 54], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10919": {"label": 3, "data": {"text": "Using [(3)H]glucosamine-labeled gastric mucosal cells, we show that stimulatory effect of beta-adrenergic agonist, isoproterenol, on mucin secretion was inhibited by EGFR kinase inhibitor, PD153035, as well as wortmannin, a specific inhibitor of PI3K.", "entity1": "mucin", "entity2": "PD153035", "span1": [133, 138], "span2": [189, 197]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9769": {"label": 5, "data": {"text": "Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors.", "entity1": "(5-HT)(1A)", "entity2": "yohimbine", "span1": [120, 130], "span2": [34, 43]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8686": {"label": 3, "data": {"text": "Our findings indicate that imatinib protects oocytes from cisplatin-induced cell death by inhibiting c-Abl kinase, which would otherwise activate TAp73-BAX-mediated apoptosis.", "entity1": "c-Abl", "entity2": "imatinib", "span1": [101, 106], "span2": [27, 35]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12379": {"label": 1, "data": {"text": "Methods: Cocktail approach was used to evaluate the influence of IR and IPC on the activities of CYP1A2, CYP2C9, CYP2E1, CYP2D6 and CYP3A4, which were reflected by the changes of pharmacokinetic parameters of five specific probe drugs: caffeine, chlorzoxazone, tolbutamide, metoprolol and midazolam, respectively.", "entity1": "CYP2E1", "entity2": "tolbutamide", "span1": [113, 119], "span2": [261, 272]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9351": {"label": 9, "data": {"text": "Expressions of insulin and PC3, but not PC2, are coordinately regulated by glucose, consistent with the important role of PC3 in regulating proinsulin processing.", "entity1": "PC2", "entity2": "glucose", "span1": [40, 43], "span2": [75, 82]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"14330": {"label": 3, "data": {"text": "Results showed that DMF increased nuclear levels of Nrf2, and both DMF and adenovirus-mediated overexpression of Nrf2 (Ad-Nrf2) decreased PAI-1, alpha-smooth muscle actin (alpha-SMA), fibronectin and type 1 collagen expression in TGF-beta-treated rat mesangial cells (RMCs) and renal fibroblast cells (NRK-49F).", "entity1": "alpha-SMA", "entity2": "DMF", "span1": [172, 181], "span2": [67, 70]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2357": {"label": 3, "data": {"text": "Thus, sorafenib may inhibit tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of Raf and Kit signaling) and/or on tumor angiogenesis (through inhibition of VEGFR and PDGFR signaling).", "entity1": "VEGFR", "entity2": "sorafenib", "span1": [196, 201], "span2": [6, 15]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4045": {"label": 3, "data": {"text": "The molecular mechanism studies suggested that neoechinulin A may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-\u03baB (NF-\u03baB) p65 and p50 subunits.", "entity1": "NF-\u03baB", "entity2": "neoechinulin A", "span1": [242, 247], "span2": [47, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2526": {"label": 8, "data": {"text": "We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and cyt b5.", "entity1": "human b5R", "entity2": "aromatic amine", "span1": [297, 306], "span2": [66, 80]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"3743": {"label": 1, "data": {"text": "Disruption of contact inhibition, which was induced by toxic AhR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or polycyclic aromatic hydrocarbons in epithelial WB-F344 cells, reduced Cx43 protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR-dependent manner.", "entity1": "AhR", "entity2": "TCDD", "span1": [346, 349], "span2": [110, 114]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, 3, 3, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1119": {"label": 3, "data": {"text": "Acetazolamide, a specific inhibitor of CA, reduces the activity of CA I and CA II from red cells.", "entity1": "CA II", "entity2": "Acetazolamide", "span1": [76, 81], "span2": [0, 13]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7220": {"label": 9, "data": {"text": "In contrast to testosterone, GnRH-induced nuclear translocation did not transcriptionally activate the androgen receptor.", "entity1": "androgen receptor", "entity2": "GnRH", "span1": [103, 120], "span2": [29, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"8338": {"label": 3, "data": {"text": "Aqueous ethanol (80%) extract of lentil hulls exhibited high antioxidant and anti-inflammatory activities preferentially inhibiting 15-LOX (IC(50), 55 \u03bcg/ml), with moderate COX-1 (IC(50), 66 \u03bcg/ml) and COX-2 (IC(50), 119 \u03bcg/ml) inhibitory effects on the COX pathway, whereas faba bean hull extracts exerted relatively mild LOX inhibitory activity.", "entity1": "15-LOX", "entity2": "ethanol", "span1": [132, 138], "span2": [8, 15]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2594": {"label": 1, "data": {"text": "In vitro data show comparable affinity to dopamine D(2), D(1) and 5-HT(2A) receptors and recently, FLX showed to be not inferior to risperidone in schizophrenic patients with predominant negative symptomatology, which was implicated with flupentixol's interaction with 5-HT(2A) and/or D(1) receptors.", "entity1": "5-HT(2A) receptors", "entity2": "FLX", "span1": [66, 84], "span2": [99, 102]}, "weak_labels": [-1, -1, -1, -1, 1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"6373": {"label": 4, "data": {"text": "The related piperidines ohmefentanyl and sufentanil and the nonselective opioid receptor agonist etorphine were less potent nociceptin receptor agonists.", "entity1": "nociceptin receptor", "entity2": "ohmefentanyl", "span1": [124, 143], "span2": [24, 36]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12712": {"label": 2, "data": {"text": "However, when coapplied with 10 micro m GABA, ivermectin potentiated the GABA-evoked current of the GAB-1/HG1A receptor, but attenuated the GABA response of the GAB-1/HG1E receptor.", "entity1": "GAB-1", "entity2": "ivermectin", "span1": [100, 105], "span2": [46, 56]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3488": {"label": 2, "data": {"text": "In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and cytochrome P450, compared to the CCl4 only group.", "entity1": "ethylmorphine-N-demethylase", "entity2": "silymarin", "span1": [120, 147], "span2": [60, 69]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13413": {"label": 9, "data": {"text": "The mRNA expression of PtdSer synthase 1 (PSS1) and PtdSer synthase 2 (PSS2) was not reduced by ethanol.", "entity1": "PSS1", "entity2": "ethanol", "span1": [42, 46], "span2": [96, 103]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"5250": {"label": 3, "data": {"text": "Synthesis and evaluation of carbamoylmethylene linked prodrugs of BMS-582949, a clinical p38\u03b1 inhibitor.", "entity1": "p38\u03b1", "entity2": "carbamoylmethylene", "span1": [89, 93], "span2": [28, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6806": {"label": 1, "data": {"text": "Thalidomide decreased the stability of TNF-mRNA and COX-2 mRNA.", "entity1": "TNF", "entity2": "Thalidomide", "span1": [39, 42], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11488": {"label": 1, "data": {"text": "RESULTS: Ketorolac was six times more active against COX-1 (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while bromfenac was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM).", "entity1": "COX-2", "entity2": "Ketorolac", "span1": [87, 92], "span2": [9, 18]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8899": {"label": 5, "data": {"text": "In the hot-plate test in mice, the antinociceptive action of the alpha 2-adrenoceptor agonist, UK 14,304, was abolished by the alpha 2-adrenoceptor antagonist, idazoxan, the potent alpha 2A-adrenoceptor antagonist, RX 821002 and the preferential alpha 2A-adrenoceptor antagonist, BRL 44408.", "entity1": "alpha 2-adrenoceptor", "entity2": "idazoxan", "span1": [127, 147], "span2": [160, 168]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13011": {"label": 2, "data": {"text": "It has been known for decades that lithium chloride (LiCl) leads to D-myo-inositol 1-phosphate accumulation on GPCR activation by inhibiting inositol monophosphatase, the final enzyme of the IP3 metabolic cascade.", "entity1": "GPCR", "entity2": "LiCl", "span1": [111, 115], "span2": [53, 57]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10695": {"label": 3, "data": {"text": "In cellular assays, lumiracoxib had an IC(50) of 0.14 microM in COX-2-expressing dermal fibroblasts, but caused no inhibition of COX-1 at concentrations up to 30 microM (HEK 293 cells transfected with human COX-1).", "entity1": "COX-2", "entity2": "lumiracoxib", "span1": [64, 69], "span2": [20, 31]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"350": {"label": 1, "data": {"text": "Affinities for the major nonadrenergic [125I]PIC binding site were highly comparable to human subtype-I1 imidazol(in)e receptor sites in the brain stem (rank order: moxonidine > clonidine > cirazoline > IDX > amiloride).", "entity1": "human subtype-I1 imidazol(in)e receptor", "entity2": "cirazoline", "span1": [88, 127], "span2": [190, 200]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15180": {"label": 2, "data": {"text": "We concluded that sophocarpine could alleviate hepatocyte steatosis and the potential mechanism might be the activated signaling pathway of AMPK.", "entity1": "AMPK", "entity2": "sophocarpine", "span1": [140, 144], "span2": [18, 30]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15626": {"label": 3, "data": {"text": "Next, nobiletin significantly decreased the levels of phospho-ERK2 and phospho-Akt in ERK2 or Akt siRNA-transfected cells concomitantly with a marked reduction on cell invasion and migration.", "entity1": "phospho-ERK2", "entity2": "nobiletin", "span1": [54, 66], "span2": [6, 15]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2893": {"label": 4, "data": {"text": "alpha(1)-Adrenoceptor antagonists were tested against the phenylephrine (alpha(1)-adrenoceptor agonist)-induced contraction in isolated hamster ureteral preparations using a functional experimental approach.", "entity1": "alpha(1)-adrenoceptor", "entity2": "phenylephrine", "span1": [73, 94], "span2": [58, 71]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9995": {"label": 3, "data": {"text": "Furthermore, h[Gly2]-GLP-2 reduced chemotherapy-induced apoptosis, decreased activation of caspase-8 and -3, and inhibited poly(ADP-ribose) polymerase cleavage in heterologous cells transfected with the GLP-2 receptor.", "entity1": "poly(ADP-ribose) polymerase", "entity2": "Gly2", "span1": [123, 150], "span2": [15, 19]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, 3, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"984": {"label": 2, "data": {"text": "Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and activating protein-1, which were increased in fructose-fed rats.", "entity1": "nuclear factor-kappaB", "entity2": "fructose", "span1": [203, 224], "span2": [275, 283]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3782": {"label": 2, "data": {"text": "Finally, we found that liver kinase B1 (LKB1) phosphorylation is required for the phillyrin-enhanced activation of AMPK in HepG2 hepatocytes.", "entity1": "AMPK", "entity2": "phillyrin", "span1": [115, 119], "span2": [82, 91]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8712": {"label": 2, "data": {"text": "The expressions of HSP70 and HO-1 were significantly (P<0.05) increased in the NaAsO2 group and reduced in the combined treatment group.", "entity1": "HO-1", "entity2": "NaAsO2", "span1": [29, 33], "span2": [79, 85]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12431": {"label": 8, "data": {"text": "This hypothesis was explored by evaluating the contributions of CYP3A4, 3A5, 3A7, and esterase enzymes in the metabolism of BDP in vitro and relating metabolism to changes in CYP3A enzyme mRNA expression via the glucocorticoid receptor in lung and liver cells.", "entity1": "esterase", "entity2": "BDP", "span1": [86, 94], "span2": [124, 127]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4637": {"label": 2, "data": {"text": "Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent activator of AhR.", "entity1": "AhR", "entity2": "TCDD", "span1": [205, 208], "span2": [169, 173]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8690": {"label": 3, "data": {"text": "Thus, imatinib and other c-Abl kinase inhibitors provide an intriguing new way to halt cisplatin-induced oocyte death in early follicles and perhaps conserve the endocrine function of the ovary against chemotherapy.Cell Death and Differentiation advance online publication, 19 April 2013; doi:10.1038/cdd.2013.31.", "entity1": "kinase", "entity2": "imatinib", "span1": [31, 37], "span2": [6, 14]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2541": {"label": 8, "data": {"text": "Polyclonal antisera to either b5R or cyt b5 significantly inhibited N-hydroxy-4-aminobiphenyl (NHOH-4-ABP) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP).", "entity1": "cyt b5", "entity2": "N-hydroxy-4-aminobiphenyl", "span1": [37, 43], "span2": [68, 93]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2208": {"label": 8, "data": {"text": "Omega class GSTs have dehydroascorbate reductase and thioltransferase activities and also catalyze the reduction of monomethylarsonate, an intermediate in the pathway of arsenic biotransformation.", "entity1": "Omega class GSTs", "entity2": "monomethylarsonate", "span1": [0, 16], "span2": [116, 134]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"2938": {"label": 1, "data": {"text": "Vardenafil has higher affinity to phosphodiesterase-5 (PDE5) than sildenafil and lower administered dosage for the treatment of erectile dysfunction.", "entity1": "phosphodiesterase-5", "entity2": "Vardenafil", "span1": [34, 53], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15306": {"label": 9, "data": {"text": "Catalase, glutathione-S-transferase and xanthine oxidase activities were not altered by atorvastatin treatment or withdrawal, as well as protein carbonyl and 4-hydroxy-2-nonenal immunoreactivity.", "entity1": "xanthine oxidase", "entity2": "atorvastatin", "span1": [40, 56], "span2": [88, 100]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3979": {"label": 2, "data": {"text": "The CYP3A4 activity could be induced 2-fold by rifampicin, whereas CYP2C9 activity remained equally high.", "entity1": "CYP3A4", "entity2": "rifampicin", "span1": [4, 10], "span2": [47, 57]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9075": {"label": 1, "data": {"text": "Hence, plasma osteocalcin is a better predictor of retinoid-induced bone effects than serum alkaline phosphatase.", "entity1": "osteocalcin", "entity2": "retinoid", "span1": [14, 25], "span2": [51, 59]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8992": {"label": 1, "data": {"text": "To clarify if the behavioral interaction between ethanol and adenosine reported previously occur centrally or due to a peripheral hemodynamic change, the effect of i.c.v.", "entity1": "adenosine", "entity2": "ethanol", "span1": [61, 70], "span2": [49, 56]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1603": {"label": 3, "data": {"text": "5-(N,N-dimethyl)-amiloride (50 microM; DMA), a concentration that selectively inhibits the NHE isoforms NHE1 and NHE2, but not NHE3, did not affect DBS.", "entity1": "NHE1", "entity2": "5-(N,N-dimethyl)-amiloride", "span1": [104, 108], "span2": [0, 26]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1113": {"label": 2, "data": {"text": "Our data also prove that indomethacin is not only an activator of CA but also antagonizes the effect of acetazolamide, a specific inhibitor of this enzyme.", "entity1": "CA", "entity2": "indomethacin", "span1": [66, 68], "span2": [25, 37]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"5823": {"label": 3, "data": {"text": "After the combined pituitary stimulation test (100 micrograms human CRH, 100 micrograms GnRH, 100 micrograms GH-releasing hormone, and 200 micrograms TRH), the ACTH peak (maximum increase at 30 min) was significantly blunted by loperamide from 9 +/- 1 to 4 +/- 1 pmol/L (P less than 0.001) and the area under the curve of ACTH from 0-120 min was reduced from 35 +/- 5 to 23 +/- 4 pmol/L.2 h (P less than 0.05).", "entity1": "ACTH", "entity2": "loperamide", "span1": [160, 164], "span2": [228, 238]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15454": {"label": 3, "data": {"text": "Of the compounds active in the present assay system, the most potent compound 7, platyphyllonol-5-O-\u03b2-d-xylopyranoside, significantly suppressed the induction of peroxisome proliferator activated receptor \u03b3 (PPAR\u03b3 and CCAAT/enhancer binding protein \u03b1 (C/EBP\u03b1) protein expression, and inhibited adipocyte differentiation induced by troglitazone, a PPAR\u03b3 agonist.", "entity1": "peroxisome proliferator activated receptor \u03b3", "entity2": "platyphyllonol-5-O-\u03b2-d-xylopyranoside", "span1": [162, 206], "span2": [81, 118]}, "weak_labels": [-1, -1, -1, 1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6633": {"label": 5, "data": {"text": "Involvement of alpha(1)-adrenoceptors was established as mydriatic responses were inhibited by systemic administration of nonselective alpha-adrenoceptor antagonists, phentolamine (0.3-3 mg/kg) and phenoxybenzamine (0.03-0.3 mg/kg), as well as by the selective alpha(1)-adrenoceptor antagonist, prazosin (0.3 mg/kg).", "entity1": "alpha-adrenoceptor", "entity2": "phenoxybenzamine", "span1": [135, 153], "span2": [198, 214]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14868": {"label": 3, "data": {"text": "Insertion of ER\u03b1 was blocked by the ER antagonist ICI 182,780 or with the protein kinase C (PKC) pathway inhibitor bisindolylmaleimide (BIS).", "entity1": "PKC", "entity2": "BIS", "span1": [92, 95], "span2": [136, 139]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10457": {"label": 8, "data": {"text": "SDH (L-serine dehydratase, EC 4.3.1.17) catalyzes the pyridoxal 5'-phosphate (PLP)-dependent dehydration of L-serine to yield pyruvate and ammonia.", "entity1": "EC 4.3.1.17", "entity2": "L-serine", "span1": [27, 38], "span2": [108, 116]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"12698": {"label": 8, "data": {"text": "Most halogenated cysteine S-conjugates are metabolized by cysteine S-conjugate beta-lyases to pyruvate, ammonia, and an alpha-chloroenethiolate (with DCVC) or an alpha-difluoroalkylthiolate (with TFEC) that may eliminate halide to give a thioacyl halide, which reacts with epsilon-amino groups of lysine residues in proteins.", "entity1": "beta-lyases", "entity2": "alpha-chloroenethiolate", "span1": [79, 90], "span2": [120, 143]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14004": {"label": 3, "data": {"text": "Cabozantinib (XL184) is a small-molecule kinase inhibitor with potent activity toward MET and VEGF receptor 2 (VEGFR2), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including RET, KIT, AXL, and FLT3.", "entity1": "VEGF receptor 2", "entity2": "XL184", "span1": [94, 109], "span2": [14, 19]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"937": {"label": 3, "data": {"text": "5-Fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of thymidylate synthase (TS).", "entity1": "TS", "entity2": "5-trifluorothymidine", "span1": [238, 240], "span2": [60, 80]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"428": {"label": 5, "data": {"text": "(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned human alpha 1D adrenoceptors.", "entity1": "human alpha 1D adrenoceptors", "entity2": "Rec 15/2739", "span1": [258, 286], "span2": [44, 55]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7368": {"label": 2, "data": {"text": "The present study examined the differential cocaine-induced activation of the cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) throughout discrete zones of analysis of the nucleus accumbens (NAc) in rats.", "entity1": "cyclic adenosine monophosphate (cAMP) response element binding protein", "entity2": "cocaine", "span1": [78, 148], "span2": [44, 51]}, "weak_labels": [-1, -1, -1, 1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1303": {"label": 1, "data": {"text": "The results reinforce previous assumptions that dopamine may interact with eicosanoid metabolism by means of D(2) receptor activation, and implicate an involvement of cPLA(2) and COX-2 in this effect.", "entity1": "cPLA(2)", "entity2": "dopamine", "span1": [167, 174], "span2": [48, 56]}, "weak_labels": [-1, -1, -1, -1, 1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15658": {"label": 1, "data": {"text": "While the function of N-type calcium channels within astrocytes is controversial, these voltage-gated calcium channels have been linked to calcium-dependent vesicular gliotransmitter release.", "entity1": "voltage-gated calcium channels", "entity2": "calcium", "span1": [88, 118], "span2": [139, 146]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7981": {"label": 1, "data": {"text": "Furthermore, U0126 (an ERK1/2 inhibitor) significantly enhanced the ISO-induced the Bax/Bcl-2 ratio, the release of cytochrome c to the cytosol fraction, and the levels of cleaved caspase-3.", "entity1": "cytochrome c", "entity2": "U0126", "span1": [116, 128], "span2": [13, 18]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1130": {"label": 3, "data": {"text": "The antipsychotic drugs sertindole and pimozide are known to prolong the QT interval on the electrocardiogram via a high affinity block of the cardiac K(+) channel known as HERG (human ether-a-go-go-related gene; erg1).", "entity1": "human ether-a-go-go-related gene", "entity2": "sertindole", "span1": [179, 211], "span2": [24, 34]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3903": {"label": 0, "data": {"text": "Insulin stimulated Pak1 activation through increasing its Thr423 phosphorylation in gut gcg-expressing cell lines, associated with increased gcg mRNA levels.", "entity1": "Pak1", "entity2": "Thr", "span1": [19, 23], "span2": [58, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12857": {"label": 1, "data": {"text": "BACKGROUND AND AIMS: Thymidylate synthase (TS) is an important enzyme for DNA synthesis and the target for 5-fluorouracil (5-FU).", "entity1": "Thymidylate synthase", "entity2": "5-FU", "span1": [21, 41], "span2": [123, 127]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2234": {"label": 3, "data": {"text": "In this study, we demonstrate significant inhibitory activity of dasatinib against both wild-type KIT and the KITD816V mutation in the nanomolar range in in vitro and cell-based kinase assays.", "entity1": "D816V", "entity2": "dasatinib", "span1": [113, 118], "span2": [65, 74]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1125": {"label": 3, "data": {"text": "CONCLUSIONS: Our results show that indomethacin, a known cyclooxygenase (COX) inhibitor, is also an activator of CA.", "entity1": "COX", "entity2": "indomethacin", "span1": [73, 76], "span2": [35, 47]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6036": {"label": 1, "data": {"text": "We conclude that despite small differences concerning the enantiomeric selectivity and affinity of rauwolscine and yohimbine, the close pharmacological identity of 5-HT receptors in rat stomach fundus and the recently cloned 5-HT2B receptor is maintained.", "entity1": "5-HT2B", "entity2": "rauwolscine", "span1": [225, 231], "span2": [99, 110]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5241": {"label": 1, "data": {"text": "Exposure of cells to 4mM NaF for 24h induced caspase-3 activation, ultrastructural alterations, and resulted in the translocation of Bax to the mitochondria and the release of cytochrome c from the mitochondrial inter-membrane space into the cytosol, indicating that fluoride-mediated apoptosis is mitochondria-dependent.", "entity1": "Bax", "entity2": "NaF", "span1": [133, 136], "span2": [25, 28]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9213": {"label": 1, "data": {"text": "We have found that certain naphthalenesulfonamides [e.g., N-6(-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7)] and phenothiazines [e.g., trifluoperazine (TFP)] induce a loss of cell-surface receptors for alpha 2-macroglobulin, and epidermal growth factor (EGF) in fibroblasts.", "entity1": "epidermal growth factor", "entity2": "trifluoperazine", "span1": [236, 259], "span2": [142, 157]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1600": {"label": 3, "data": {"text": "Nevertheless, coperfusion with 0.1 and 0.3 mM 5-nitro-2-(3-phenylpropylamino) benzoic acid, which inhibits the cystic fibrosis transmembrane conductor regulator (CFTR), dose dependently inhibited S3226-induced DBS.", "entity1": "cystic fibrosis transmembrane conductor regulator", "entity2": "5-nitro-2-(3-phenylpropylamino) benzoic acid", "span1": [111, 160], "span2": [46, 90]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"839": {"label": 3, "data": {"text": "Felbamate produced a rapid, concentration-dependent block of currents evoked by 50 microM NMDA and 10 microM glycine in human embryonic kidney 293 cells expressing the rat NR1a subunit, and either the NR2A, NR2B or NR2C subunits; the IC50 values for block were 2.6, 0.52 and 2.4 mM, respectively (holding potential, - 60 mV).", "entity1": "NR2B", "entity2": "Felbamate", "span1": [207, 211], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"4298": {"label": 8, "data": {"text": "Compound 6 stimulated OATP1B3-mediated estradiol 17\u03b2-glucuronide uptake by increasing the apparent affinity of OATP1B3 for its substrate.", "entity1": "OATP1B3", "entity2": "estradiol 17\u03b2-glucuronide", "span1": [111, 118], "span2": [39, 64]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"8609": {"label": 3, "data": {"text": "Serum markers of liver damage (AST, ALT, ALP and Bilirubin) were increased by CCl4 and TAA intoxication (p<0.001), whereas co-treatment with NAC reversed such changes (p<0.001).", "entity1": "ALT", "entity2": "NAC", "span1": [36, 39], "span2": [141, 144]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11382": {"label": 1, "data": {"text": "Thus, the cranio-selective vasoconstriction elicited by ergotamine in dogs is predominantly mediated by 5-HT1B receptors as well as alpha2A/2C-adrenoceptor subtypes and, to a lesser extent, by alpha1-adrenoceptors.", "entity1": "5-HT1B", "entity2": "ergotamine", "span1": [104, 110], "span2": [56, 66]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8482": {"label": 0, "data": {"text": "Interestingly, insulin treatment of \u03b1XBPKD cells reduced tyrosine phosphorylation of IRS-1 (pY(896)), and phosphorylation of Akt, while enhancing serine phosphorylation (pS(307)) of IRS-1.", "entity1": "IRS-1", "entity2": "serine", "span1": [182, 187], "span2": [146, 152]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8832": {"label": 3, "data": {"text": "RESULTS: By Western blot analysis of spinal cord tissues, we have demonstrated that treatment with bioactive RS -GRA significantly decreased nuclear factor (NF)-kB translocation, pro-inflammatory cytokine production such as interleukin-1\u03b2 (IL-1\u03b2), and apoptosis (Bax and caspase 3 expression).", "entity1": "IL-1\u03b2", "entity2": "RS -GRA", "span1": [240, 245], "span2": [109, 116]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"3985": {"label": 8, "data": {"text": "Mammalian ALDH1B1, another mitochondrial enzyme sharing 72% identity with ALDH2, is also capable of metabolizing acetaldehyde but has a tissue distribution and pattern of activity distinct from that of ALDH2.", "entity1": "Mammalian ALDH1B1", "entity2": "acetaldehyde", "span1": [0, 17], "span2": [113, 125]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"11333": {"label": 1, "data": {"text": "In the present study, we measured the enzyme activity of thymidine kinase (TK), thymidine phosphorylase (TP) and thymidilate synthase (TS) in human cancer xenografts to investigate the contribution of these enzymes to the sensitivity of TAS-102.", "entity1": "thymidine phosphorylase", "entity2": "TAS-102", "span1": [80, 103], "span2": [237, 244]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8335": {"label": 5, "data": {"text": "Rolapitant and netupitant are other NK1 receptor antagonists that are currently in phase III clinical trials.", "entity1": "NK1 receptor", "entity2": "Rolapitant", "span1": [36, 48], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15920": {"label": 1, "data": {"text": "Moreover, the active permethylated vancomycin aglycon derivatives examined exhibit VanB VRE antimicrobial activity at levels that approach (typically within 2-fold) their activity against sensitive bacteria.", "entity1": "VanB", "entity2": "vancomycin", "span1": [83, 87], "span2": [35, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13233": {"label": 1, "data": {"text": "Down-regulation of GRIP1 by glutamate was blocked by carbobenzoxyl-leucinyl-leucinyl-leucinal (MG132), a proteasome inhibitor and by expression of K48R-ubiquitin, a dominant negative form of ubiquitin.", "entity1": "GRIP1", "entity2": "carbobenzoxyl-leucinyl-leucinyl-leucinal", "span1": [19, 24], "span2": [53, 93]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4243": {"label": 8, "data": {"text": "As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and xanthine oxidase was identified as the likely source of TES-stimulated superoxide production.", "entity1": "xanthine oxidase", "entity2": "superoxide", "span1": [115, 131], "span2": [186, 196]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"6130": {"label": 5, "data": {"text": "We have investigated the effects of CP-99,994 [(+)-(2s,3s)-3-(2-methoxybenzylamino)-2-phenylpiperidine], a tachykinin NK1 receptor antagonist, HOE 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2 receptor antagonist, and ketotifen (4-(1-methyl-4-piperidylidene)4 H-benzo[4,5]cycloheptal[1,2-b]thiophen-10(9H)-one hydrogen fumarate), a histamine H1 receptor antagonist with mast cell-stabilizing properties, on microvascular leakage induced by gaseous formaldehyde.", "entity1": "tachykinin NK1 receptor", "entity2": "[(+)-(2s,3s)-3-(2-methoxybenzylamino)-2-phenylpiperidine]", "span1": [107, 130], "span2": [46, 103]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2410": {"label": 2, "data": {"text": "Extracellular L-arginine also dose-dependently increased NO release and arginase activity.", "entity1": "arginase", "entity2": "L-arginine", "span1": [72, 80], "span2": [14, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7533": {"label": 8, "data": {"text": "10), is an 18-kDa integral nuclear membrane protein that belongs to a superfamily of membrane-associated proteins in eicosanoid and glutathione metabolism that includes 5-lipoxygenase-activating protein, microsomal glutathione S-transferases (MGSTs), and microsomal prostaglandin E synthase 1 (ref.", "entity1": "MGSTs", "entity2": "eicosanoid", "span1": [243, 248], "span2": [117, 127]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12321": {"label": 2, "data": {"text": "Ribavirin also enhanced recruitment of CDK9 (cyclin-dependent kinase 9) and AFF4 to F7.", "entity1": "CDK9", "entity2": "Ribavirin", "span1": [39, 43], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6128": {"label": 1, "data": {"text": "The increase in vascular permeability induced by formaldehyde in the rat airway was mediated predominantly by NK1 receptor stimulation.", "entity1": "NK1 receptor", "entity2": "formaldehyde", "span1": [110, 122], "span2": [49, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5669": {"label": 2, "data": {"text": "Further we found stimulation of FAS-expression as a result of epigenetic DNA demethylation that was due to down-regulation of DNMT1, which was rescued by re-isoprenylation by both geranylgeranyl-pyrophosphate and farnesylpyrophosphate.", "entity1": "FAS", "entity2": "geranylgeranyl-pyrophosphate", "span1": [32, 35], "span2": [180, 208]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9967": {"label": 3, "data": {"text": "Selective COX-2 inhibitors, such as meloxicam, celecoxib (SC-58635), and rofecoxib (MK-0966), are NSAIDs that have been modified chemically to preferentially inhibit COX-2 but not COX-1.", "entity1": "COX-2", "entity2": "MK-0966", "span1": [166, 171], "span2": [84, 91]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7715": {"label": 5, "data": {"text": "Palonosetron is a second-generation serotonin 5-HT3 receptor antagonist, with a distinct pharmacological profile that differs from first-generation 5-HT3 receptor antagonists.", "entity1": "serotonin 5-HT3 receptor", "entity2": "Palonosetron", "span1": [36, 60], "span2": [0, 12]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10857": {"label": 1, "data": {"text": "Most of the tested H(2)R agonists and imidazole-based H(3)R ligands show micromolar-to-nanomolar range hH(4)R affinity, and these ligands exert different intrinsic hH(4)R activities, ranging from full agonists to inverse agonists.", "entity1": "H(3)R", "entity2": "imidazole", "span1": [54, 59], "span2": [38, 47]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6182": {"label": 3, "data": {"text": "Based on these results, we conclude that the NSAIDs ibuprofen and salicylic acid inhibit cAMP-mediated Cl- secretion in human colonic and airway epithelia via a direct inhibition of CFTR Cl- channels as well as basolateral membrane K+ channels.", "entity1": "Cl- channels", "entity2": "salicylic acid", "span1": [187, 199], "span2": [66, 80]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1619": {"label": 2, "data": {"text": "We examined if subcutaneous decitabine could increase HbF levels and improve SSD pathophysiology without cytotoxicity.", "entity1": "HbF", "entity2": "decitabine", "span1": [54, 57], "span2": [28, 38]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7293": {"label": 3, "data": {"text": "PFD leads to a reduction of TGF-beta2 mRNA levels and of the mature TGF-beta2 protein due to decreased expression and direct inhibition of the TGF-beta pro-protein convertase furin.", "entity1": "pro-protein convertase", "entity2": "PFD", "span1": [152, 174], "span2": [0, 3]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1]},
	"5294": {"label": 3, "data": {"text": "Thus prolonged activation of NMDA receptors in hippocampal neurons reduced GABAR \u03b4 subunit expression through Ca2+ entry and at least in part by ERK1/2 activation.", "entity1": "GABAR \u03b4 subunit", "entity2": "Ca2+", "span1": [75, 90], "span2": [110, 114]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3390": {"label": 1, "data": {"text": "The effects of amphetamine (AMPH) and cocaine (COC), for example, depend on the ability to increase dopamine in the synapse, by effects on either the plasma membrane transporter DAT or the vesicular transporter for monoamine storage, VMAT2.", "entity1": "DAT", "entity2": "AMPH", "span1": [178, 181], "span2": [28, 32]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"14681": {"label": 3, "data": {"text": "In vitro, GSK1292263 demonstrated little/weak inhibition (IC50 values >30 \u03bcM) towards CYPs (CYP1A2, 2C9, 2C19, 2D6, 3A4), Pgp, OATP1B3, or OCT2.", "entity1": "2C19", "entity2": "GSK1292263", "span1": [105, 109], "span2": [10, 20]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1574": {"label": 3, "data": {"text": "The BuChE inhibitory activity is only significant in compounds 11 and 14, ten-fold less active than tacrine.", "entity1": "BuChE", "entity2": "tacrine", "span1": [4, 9], "span2": [100, 107]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12518": {"label": 1, "data": {"text": "The uncharged estramustine bound to both tubulin and MAPs, but no effects were seen on microtubule assembly, the composition of coassembled MAPs or the microtubule morphology.", "entity1": "tubulin", "entity2": "estramustine", "span1": [41, 48], "span2": [14, 26]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13865": {"label": 3, "data": {"text": "Mitiglinide reduced fasting plasma glucose and GA levels after 4 weeks and Hb(A1c) levels after 8 weeks.", "entity1": "GA", "entity2": "Mitiglinide", "span1": [47, 49], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4965": {"label": 4, "data": {"text": "In the present study, we identified amprenavir, a widely used HIV PI, as a potent PXR-selective agonist.", "entity1": "PXR", "entity2": "amprenavir", "span1": [82, 85], "span2": [36, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4265": {"label": 2, "data": {"text": "Interestingly, ursolic acid increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of GSK3\u03b2 at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells.", "entity1": "AMPK", "entity2": "ursolic acid", "span1": [61, 65], "span2": [15, 27]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4550": {"label": 8, "data": {"text": "Given these findings, a unified PK model including the inhibition of MAO-A- and CYP2D6-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.", "entity1": "CYP2D6", "entity2": "5-MeO-DMT", "span1": [237, 243], "span2": [97, 106]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"4334": {"label": 3, "data": {"text": "Suppression of Src/ERK and GSK-3/\u03b2-catenin signaling by pinosylvin inhibits the growth of human colorectal cancer cells.", "entity1": "\u03b2-catenin", "entity2": "pinosylvin", "span1": [33, 42], "span2": [56, 66]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10003": {"label": 8, "data": {"text": "The purpose of this study was to determine whether rat outer medullary collecting duct (OMCD) secretes Cl- and whether transepithelial Cl- transport occurs, in part, through Cl- uptake across the basolateral membrane mediated by NKCC1 in series with Cl- efflux across the apical membrane.", "entity1": "NKCC1", "entity2": "Cl-", "span1": [229, 234], "span2": [250, 253]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"2997": {"label": 1, "data": {"text": "Catalytic-site affinities for cGMP, vardenafil, sildenafil, tadalafil, or 3-isobutyl-1-methylxanthine (IBMX) were respectively weakened 14-, 123-, 30-, 51-, and 43-fold for Y612A; 63-, 511-, 43-, 95- and 61-fold for Q817A; and 59-, 448-, 71-, 137-, and 93-fold for F820A.", "entity1": "Q817A", "entity2": "IBMX", "span1": [216, 221], "span2": [103, 107]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1843": {"label": 3, "data": {"text": "Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (BLT-4), blocked ABCA1-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM).", "entity1": "SR-BI", "entity2": "1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea", "span1": [197, 202], "span2": [29, 72]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14300": {"label": 0, "data": {"text": "Studies have indicated that the three-dimensional structure and the domains of HuBChE (acyl pocket, lip of the active center gorge, and the anionic substrate-binding domain) that are critical for the binding of substrate are also essential for the selectivity and binding of inhibitors including OPs.", "entity1": "HuBChE", "entity2": "acyl", "span1": [79, 85], "span2": [87, 91]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"6366": {"label": 4, "data": {"text": "The related piperidines ohmefentanyl and sufentanil and the nonselective opioid receptor agonist etorphine were less potent nociceptin receptor agonists.", "entity1": "nociceptin receptor", "entity2": "sufentanil", "span1": [124, 143], "span2": [41, 51]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9777": {"label": 4, "data": {"text": "The nonselective opioid receptor antagonist, naloxone (3 mg/kg, i.m. ), attenuated the antitussive effects of codeine or SB 227122, indicating that the antitussive activity of both compounds is opioid receptor-mediated.", "entity1": "opioid receptor", "entity2": "SB 227122", "span1": [17, 32], "span2": [121, 130]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5164": {"label": 8, "data": {"text": "At a substrate concentration of 20\u2009\u00b5M, the most active HFC glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300\u2009\u00b5M UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.", "entity1": "UGT1A10", "entity2": "HFC", "span1": [90, 97], "span2": [55, 58]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 8, -1, -1, -1]},
	"1017": {"label": 1, "data": {"text": "In COS cells transfected with alpha(1b) adrenoceptor cDNA and in DDT(1) MF-2 cells which express native alpha(1B) adrenoceptors, [(3)H]-prazosin was displaced by unlabelled prazosin in a normal equilibrium process, with no prazosin paradox in concentrations up to 10(-6) M. In DDT(1) MF-2 cells, [(3)H]-prazosin was displaced likewise by a series of alpha(1) adrenergic agonists, none of which increased the binding of [(3)H]-prazosin.", "entity1": "alpha(1B) adrenoceptors", "entity2": "[(3)H]-prazosin", "span1": [104, 127], "span2": [129, 144]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"204": {"label": 1, "data": {"text": "The affinities of a number of alpha 1-adrenoceptor antagonists were determined by displacement of [3H]-prazosin binding from cloned human alpha 1A-adrenoceptors (previously designated cloned alpha 1c subtype), alpha 1B alpha 1D and rat alpha 1D-adrenoceptors, stably expressed in rat-1 fibroblasts.", "entity1": "rat alpha 1D-adrenoceptors", "entity2": "[3H]-prazosin", "span1": [232, 258], "span2": [98, 111]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7108": {"label": 3, "data": {"text": "Coadministration of reboxetine and the dopamine transporter blocker GBR 12909 also increased spontaneous locomotor activity.", "entity1": "dopamine transporter", "entity2": "GBR 12909", "span1": [39, 59], "span2": [68, 77]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"3520": {"label": 3, "data": {"text": "We studied mouse osteoblasts alone or in a co-culture with HGC to determine whether TZD inhibition of aromatase plays a role in their effects on bone metabolism.", "entity1": "aromatase", "entity2": "TZD", "span1": [102, 111], "span2": [84, 87]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1110": {"label": 2, "data": {"text": "Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action.", "entity1": "carbonic anhydrase", "entity2": "Indomethacin", "span1": [23, 41], "span2": [0, 12]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10877": {"label": 3, "data": {"text": "Irinotecan (CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) has exhibited clinical activities against a broad spectrum of carcinomas by inhibiting DNA topoisomerase I (Topo I).", "entity1": "Topo I", "entity2": "7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin", "span1": [196, 202], "span2": [20, 86]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9531": {"label": 8, "data": {"text": "Methylenetetrahydrofolate reductase deficiency impairs methyltetrahydrofolate synthesis, defects in cytosolic reduction of hydroxocobalamin (CblC/D) impair the synthesis of both methyl- and adenosyl cobalamin and deficiencies of methionine synthase (CblE/G) are associated with defective methyl cobalamin synthesis.", "entity1": "methionine synthase", "entity2": "methyl cobalamin", "span1": [229, 248], "span2": [288, 304]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"302": {"label": 2, "data": {"text": "It is concluded that D-1997 contracts the canine basilar artery by stimulating 5-HT1-like receptors unrelated to either the 5-HT1A or 5-HT1B receptor subtypes.", "entity1": "5-HT1A", "entity2": "D-1997", "span1": [124, 130], "span2": [21, 27]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2441": {"label": 8, "data": {"text": "METHODS: Cyclooxygenase activity and selectivity was determined in vitro by measuring prostaglandin E(2) (PGE(2)) production following incubation of varying concentrations of NSAID with human recombinant COX-1 or COX-2 and arachidonic acid.", "entity1": "Cyclooxygenase", "entity2": "prostaglandin E(2)", "span1": [9, 23], "span2": [86, 104]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"7536": {"label": 8, "data": {"text": "10), is an 18-kDa integral nuclear membrane protein that belongs to a superfamily of membrane-associated proteins in eicosanoid and glutathione metabolism that includes 5-lipoxygenase-activating protein, microsomal glutathione S-transferases (MGSTs), and microsomal prostaglandin E synthase 1 (ref.", "entity1": "MGSTs", "entity2": "glutathione", "span1": [243, 248], "span2": [132, 143]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7364": {"label": 1, "data": {"text": "The temporal and anatomical determinants of cocaine-induced CREB activity may indicate functional differences among NAc shell subregions and suggest the involvement of CREB in early and late cocaine effects.", "entity1": "CREB", "entity2": "cocaine", "span1": [168, 172], "span2": [191, 198]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13541": {"label": 2, "data": {"text": "The transcriptional activity of torafugu PPARalpha1 was enhanced 4.5- and 11.5-fold by Wy-14643 and 5,8,11,14-eicosatetraynoic acid (ETYA) each at 10 microM, respectively, whereas that of PPARalpha2, 4.5- and 7.3-fold at the same concentration of the respective ligands, respectively.", "entity1": "PPARalpha2", "entity2": "Wy-14643", "span1": [188, 198], "span2": [87, 95]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13789": {"label": 3, "data": {"text": "The following TK blockers for treatment of various human tumors are in clinical development: Lapatinib (Lapatinib ditosylate, Tykerb, GW-572016), Canertinib (CI-1033), Zactima (ZD6474), Vatalanib (PTK787/ZK 222584), Sorafenib (Bay 43-9006, Nexavar), and Leflunomide (SU101, Arava).", "entity1": "TK", "entity2": "Nexavar", "span1": [14, 16], "span2": [240, 247]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5052": {"label": 3, "data": {"text": "Blockade of JAK and ERK pathways with AG490 and U0126, respectively, abrogated the myocardial infarct size reduction by NDP-\u03b1-MSH.", "entity1": "JAK", "entity2": "AG490", "span1": [12, 15], "span2": [38, 43]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14165": {"label": 5, "data": {"text": "In the present study we tested whether propranolol, a \u03b2-receptor antagonist commonly used as antihypertensive drug, could ameliorate the cognitive impairments and increases in AD-related markers shown by the senescence-accelerated mouse prone-8 (SAMP8).", "entity1": "\u03b2-receptor", "entity2": "propranolol", "span1": [54, 64], "span2": [39, 50]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12622": {"label": 1, "data": {"text": "In addition, three IP ligands, iloprost, carbacyclin and isocarbacyclin, and one TP ligand, STA2, bound to this receptor with Ki values comparable to the Ki values of these compounds for the IP and TP receptors, respectively.", "entity1": "IP", "entity2": "isocarbacyclin", "span1": [19, 21], "span2": [57, 71]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6935": {"label": 8, "data": {"text": "When the growth condition was shifted from aerobic to anaerobic, the increased level of succinate in SDH1 disruptants was no longer observed, whereas the decreased level of succinate in the KGD1 diruptant was still observed.", "entity1": "KGD1", "entity2": "succinate", "span1": [190, 194], "span2": [173, 182]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14404": {"label": 3, "data": {"text": "Herein, we report the identification and characterization of 3-(5-tert-butyl-isoxazol-3-yl)-2-[(3-chloro-phenyl)-hydrazono]-3-oxo-propionitrile (ESI-09), a novel noncyclic nucleotide EPAC antagonist that is capable of specifically blocking intracellular EPAC-mediated Rap1 activation and Akt phosphorylation, as well as EPAC-mediated insulin secretion in pancreatic \u03b2 cells.", "entity1": "Akt", "entity2": "3-(5-tert-butyl-isoxazol-3-yl)-2-[(3-chloro-phenyl)-hydrazono]-3-oxo-propionitrile", "span1": [288, 291], "span2": [61, 143]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1793": {"label": 3, "data": {"text": "Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and PKI166 and GW572016, both examples of dual kinase inhibitors (inhibiting epidermal growth factor receptor and Her2).", "entity1": "Her2", "entity2": "PKI166", "span1": [242, 246], "span2": [132, 138]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15953": {"label": 1, "data": {"text": "4-Hydroxytamoxifen (OHT, tamoxifen's active form) failed to prevent E2-induced proteolysis of cyclin E and migration, but rather triggered cyclin E cleavage coincident with augmented migration.", "entity1": "cyclin E", "entity2": "tamoxifen", "span1": [139, 147], "span2": [25, 34]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3199": {"label": 3, "data": {"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1).", "entity1": "EC 4.2.1.1", "entity2": "p-coumaric acid", "span1": [286, 296], "span2": [87, 102]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"6521": {"label": 3, "data": {"text": "There was a dose-dependent decrease in plasma renin activity, Ang I, and Ang II following single doses of Aliskiren starting with 40 mg. Inhibition was still marked and significant after repeated dosing with maximal decreases in Ang II levels by 89% and 75% on Days 1 and 8, respectively, when the highest dose of Aliskiren was compared with placebo.", "entity1": "renin", "entity2": "Aliskiren", "span1": [46, 51], "span2": [106, 115]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15033": {"label": 8, "data": {"text": "All the compounds were evaluated for their anti-tumor activity against MCF-7, A549 and B16-F10 tumor cell lines as well as cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) inhibitory activity of murine macrophage RAW 264.7 cell line.", "entity1": "cyclooxygenase-2", "entity2": "prostaglandin E2", "span1": [123, 139], "span2": [156, 172]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"60": {"label": 3, "data": {"text": "Enalkiren has been shown to produce dose-related suppression of plasma renin activity (PRA) and angiotensin II when administered intravenously.", "entity1": "renin", "entity2": "Enalkiren", "span1": [71, 76], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"15222": {"label": 3, "data": {"text": "In HaCaT cells, buthanol and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-\u03b1 (TNF- \u03b1).", "entity1": "TNF- \u03b1", "entity2": "clerosterol", "span1": [365, 371], "span2": [123, 134]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7782": {"label": 2, "data": {"text": "We also investigated the epigenetic status of NIS promoter after PJ34 treatment in TPC1 cell line: in addition to an increase of histone modification activation marks (H3K9K14ac, H3K4me3), surprisingly we observed also an increase of H3K27me3, a classical repressive mark.", "entity1": "histone modification activation marks", "entity2": "PJ34", "span1": [129, 166], "span2": [65, 69]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15741": {"label": 3, "data": {"text": "Wattakaka volubilis steroidal glycoside mixture (WVSM) and PPG (1-50\u03bcM) significantly inhibited the COX-2 and iNOS enzymes resulting in low levels of PGE2 and NO in LPS-induced RAW 264.7 macrophage cells.", "entity1": "iNOS", "entity2": "PPG", "span1": [110, 114], "span2": [59, 62]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4640": {"label": 2, "data": {"text": "Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent activator of AhR.", "entity1": "CYP1A1", "entity2": "pelargonidin", "span1": [50, 56], "span2": [11, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7144": {"label": 1, "data": {"text": "A 46-amino acid segment in phosphodiesterase-5 GAF-B domain provides for high vardenafil potency over sildenafil and tadalafil and is involved in phosphodiesterase-5 dimerization.", "entity1": "phosphodiesterase-5", "entity2": "tadalafil", "span1": [146, 165], "span2": [117, 126]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4762": {"label": 3, "data": {"text": "Previously, we have found that BRN-103, a nicotinamide derivative, inhibits vascular endothelial growth factor (VEGF)-mediated angiogenesis signaling in human endothelial cells.", "entity1": "VEGF", "entity2": "nicotinamide", "span1": [112, 116], "span2": [42, 54]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6443": {"label": 2, "data": {"text": "This study demonstrates that CB1093 and clenbuterol stimulate NGF levels in vitro and that AP-1 binding could be a commonality between the mechanism of NGF induction of these two compounds.", "entity1": "NGF", "entity2": "CB1093", "span1": [152, 155], "span2": [29, 35]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9910": {"label": 2, "data": {"text": "It is proposed that the UCP-3 gene is regulated in skeletal muscle during lactation in response to changes in circulating free fatty acids by mechanisms involving activation of PPARs.", "entity1": "PPARs", "entity2": "fatty acids", "span1": [177, 182], "span2": [127, 138]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"269": {"label": 0, "data": {"text": "Drosophila GABA-gated chloride channel: modified [3H]EBOB binding site associated with Ala-->Ser or Gly mutants of Rdl subunit.", "entity1": "Rdl", "entity2": "Ser", "span1": [115, 118], "span2": [93, 96]}, "weak_labels": [-1, -1, 0, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6391": {"label": 4, "data": {"text": "In alpha(2A)-adrenoceptor transfected cells the rank order of agonist potency was A-54741 (mean pEC(50)=8.96)>dexmedetomidine (8.88)>UK-14304 (8.42)>B-HT 920 (7.05)>noradrenaline (6.92).", "entity1": "alpha(2A)-adrenoceptor", "entity2": "dexmedetomidine", "span1": [3, 25], "span2": [110, 125]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7193": {"label": 8, "data": {"text": "KIEs were measured on the arsenolysis of 5'-methylthioadenosine (MTA) catalyzed by MTAP and were corrected for the forward commitment to catalysis.", "entity1": "MTAP", "entity2": "5'-methylthioadenosine", "span1": [83, 87], "span2": [41, 63]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"8885": {"label": 3, "data": {"text": "By \"working upwards\" from mTOR, we observed that TCDD inhibited endogenous and IGF-I-induced AKT and ERK activation by interfering with tyrosine phosphorylation of insulin receptor substrate 1.", "entity1": "AKT", "entity2": "TCDD", "span1": [93, 96], "span2": [49, 53]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"2948": {"label": 0, "data": {"text": "The results quantify the role of PDE5 catalytic-site residues for cGMP and inhibitors, indicate that Tyr-612, Gln-817, and Phe-820 are the most important cGMP or inhibitor contacts studied, and identify residues that contribute to selectivity among different classes of inhibitors.", "entity1": "PDE5", "entity2": "Gln", "span1": [33, 37], "span2": [110, 113]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8377": {"label": 3, "data": {"text": "Although there was no change in the levels of insulin receptor (IR), Akt (protein kinase B) and glucose transporter-4 (GLUT4) messenger RNA, BPA significantly decreased the IR, Akt and GLUT4 protein levels (both plasma membrane and cytosolic fraction) of the gastrocnemius muscle.", "entity1": "Akt", "entity2": "BPA", "span1": [177, 180], "span2": [141, 144]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"9015": {"label": 4, "data": {"text": "The limitation of SRF by diazepam was not prevented by inverse or partial agonists at the BDZ receptor, including Ro 15-1788 and the beta CCs.", "entity1": "BDZ receptor", "entity2": "Ro 15-1788", "span1": [90, 102], "span2": [114, 124]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"13331": {"label": 9, "data": {"text": "Fluoxetine affected mainly the hSERT transport rate by reducing the availability of the transporter in the membrane with no significant alteration of either the total hSERT protein content or the hSERT mRNA level.", "entity1": "hSERT", "entity2": "Fluoxetine", "span1": [167, 172], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"13745": {"label": 1, "data": {"text": "Inhibition of (+)-[(3)H]isradipine binding to Ca(v)1.2DHP(-/-) (predominantly Ca(v)1.3) and wild-type (predominantly Ca(v)1.2) brain membranes by unlabeled DHPs revealed a 3- to 4-fold selectivity of nitrendipine and nifedipine for the Ca(v)1.2 binding pocket, a finding further confirmed with heterologously expressed channels.", "entity1": "Ca(v)1.2", "entity2": "(+)-[(3)H]isradipine", "span1": [117, 125], "span2": [14, 34]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11004": {"label": 1, "data": {"text": "In this study, antidepressants with selectivity for the noradrenaline transporter (reboxetine and desipramine), or the serotonin transporter (fluoxetine and clomipramine) were examined in terms of their ability to promote an anti-inflammatory cytokine phenotype in human blood.", "entity1": "serotonin transporter", "entity2": "fluoxetine", "span1": [119, 140], "span2": [142, 152]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, 9]},
	"1826": {"label": 8, "data": {"text": "QR2 catalyzes the two-electron reduction of menadione via the oxidation of N-alkylated or N-ribosylated nicotinamides.", "entity1": "QR2", "entity2": "menadione", "span1": [0, 3], "span2": [44, 53]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"4865": {"label": 2, "data": {"text": "Saturated palmitic and stearic acids increased ceramides, up-regulated PTP1B, and had AKt and PTP1B phosphorylation at Ser 50 impaired.", "entity1": "PTP1B", "entity2": "palmitic and stearic acids", "span1": [71, 76], "span2": [10, 36]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5583": {"label": 8, "data": {"text": "PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to 5-fluorouracil (5-FU) by thymidine phosphorylase (TP) inside target tissues.", "entity1": "TP", "entity2": "capecitabine", "span1": [121, 123], "span2": [41, 53]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1]},
	"14145": {"label": 1, "data": {"text": "In rat striatum and nucleus accumbens, mianserin stimulated [35S]GTPgammaS binding in a nor-BNI-sensitive manner with maximal effects lower than those of the full kappa-opioid agonists (-)-U50,488 and dynorphin A.", "entity1": "kappa-opioid", "entity2": "mianserin", "span1": [163, 175], "span2": [39, 48]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12551": {"label": 1, "data": {"text": "Intracellular protein-bound [57Co]Cbl fractionated with methionine synthase (MS) and methylmalonyl-CoA mutase (MU) activity.", "entity1": "methionine synthase", "entity2": "[57Co]Cbl", "span1": [56, 75], "span2": [28, 37]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11581": {"label": 1, "data": {"text": "As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved HbA(1c) to a significantly greater extent than placebo when added to metformin or pioglitazone and was noninferior to glipizide when added to metformin.", "entity1": "HbA(1c)", "entity2": "glipizide", "span1": [128, 135], "span2": [246, 255]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6248": {"label": 1, "data": {"text": "Eletriptan, like sumatriptan, zolmitriptan, naratriptan and rizatriptan had highest affinity for the human 5-HT1B, 5-HT1D and putative 5-ht1f receptor.", "entity1": "5-HT1D", "entity2": "zolmitriptan", "span1": [115, 121], "span2": [30, 42]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15985": {"label": 3, "data": {"text": "METHODS: After 1\u00a0month of HFD alone, the mice were given the DPP4 inhibitor vildagliptin for a further 11\u00a0months.", "entity1": "DPP4", "entity2": "vildagliptin", "span1": [61, 65], "span2": [76, 88]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"76": {"label": 3, "data": {"text": "Aspirin (ASA) and other non-steroidal anti-inflammatory drugs, which are cyclooxygenase (COX) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients.", "entity1": "COX", "entity2": "Aspirin", "span1": [89, 92], "span2": [0, 7]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1406": {"label": 8, "data": {"text": "Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astrocytes.", "entity1": "iNOS", "entity2": "NO", "span1": [135, 139], "span2": [77, 79]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"2955": {"label": 0, "data": {"text": "Cocrystal structures of PDE5 catalytic (C) domain with inhibitors reveal a hydrogen bond and hydrophobic interactions with Tyr-612, hydrogen bonds with Gln-817, a hydrophobic clamp formed by Phe-820 and Val-782, and contacts with His-613, Leu-765, and Phe-786 [Sung et al.", "entity1": "PDE5 catalytic (C) domain", "entity2": "Leu", "span1": [24, 49], "span2": [239, 242]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9211": {"label": 1, "data": {"text": "We have found that certain naphthalenesulfonamides [e.g., N-6(-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7)] and phenothiazines [e.g., trifluoperazine (TFP)] induce a loss of cell-surface receptors for alpha 2-macroglobulin, and epidermal growth factor (EGF) in fibroblasts.", "entity1": "EGF", "entity2": "phenothiazines", "span1": [261, 264], "span2": [120, 134]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"2866": {"label": 8, "data": {"text": "Specifically, hGSTA4 cells had significantly higher GSH concentrations when exposed to 5-15 microM 4-HNE, but not at 20 microM 4-HNE, suggesting extensive GSH utilization at high concentrations of 4-HNE.", "entity1": "hGSTA4", "entity2": "4-HNE", "span1": [14, 20], "span2": [99, 104]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"15274": {"label": 4, "data": {"text": "Effects of SSR125543 were compared to those of the 5-HT reuptake inhibitor, paroxetine (10\u00a0mg/kg/day), and the partial N-methyl-D-aspartate (NMDA) receptor agonist, D-cycloserine (10\u00a0mg/kg/day), two compounds which have demonstrated clinical efficacy against PTSD.", "entity1": "N-methyl-D-aspartate (NMDA) receptor", "entity2": "D-cycloserine", "span1": [119, 155], "span2": [165, 178]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11424": {"label": 1, "data": {"text": "PCR demonstrated a correlation between dCK expression and gemcitabine sensitivity, whereas expression of TS, DHFR, and GARFT was predictive of pemetrexed chemosensitivity.", "entity1": "dCK", "entity2": "gemcitabine", "span1": [39, 42], "span2": [58, 69]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13613": {"label": 3, "data": {"text": "Sorafenib and sunitinib are synthetic, orally active agents shown to directly inhibit vascular endothelial growth factor receptors -2 and -3 (VEGFR-2, VEGFR-3) and platelet-derived growth factor receptor beta (PDGFR-beta), while temsirolimus is an mTOR inhibitor.", "entity1": "VEGFR-2", "entity2": "sunitinib", "span1": [142, 149], "span2": [14, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1662": {"label": 9, "data": {"text": "RESULTS: In vivo, loss and recovery of the righting reflex required similar times after intraperitoneal injection of etomidate in wild-type and in alpha2A-receptor-deficient mice, indicating that the hypnotic effect of etomidate in mice does not require the alpha2A-receptor subtype.", "entity1": "alpha2A-receptor", "entity2": "etomidate", "span1": [258, 274], "span2": [219, 228]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"728": {"label": 9, "data": {"text": "Human and rat renin and angiotensinogen genes were downregulated in dTGR and were increased by losartan and cilazapril treatments, whereas no changes in the expression of rat ACE and AT1A receptor genes were observed.", "entity1": "AT1A", "entity2": "losartan", "span1": [183, 187], "span2": [95, 103]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13831": {"label": 1, "data": {"text": "Mammalian glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of l-glutamate to 2-oxoglutarate using NAD(P)(+) as coenzyme.", "entity1": "Mammalian glutamate dehydrogenase", "entity2": "NAD(P)(+)", "span1": [0, 33], "span2": [157, 166]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"9673": {"label": 3, "data": {"text": "Inhibition of cPLA2 translocation and leukotriene C4 secretion by fluticasone propionate in exogenously activated human eosinophils.", "entity1": "cPLA2", "entity2": "fluticasone propionate", "span1": [14, 19], "span2": [66, 88]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9563": {"label": 2, "data": {"text": "The observed inhibition on IFN-gamma, GM-CSF, and IL-3 mRNA was blocked by the selective beta2AR antagonist ICI 118,551 (10(-6) M) and by timolol (10(-6) M), a nonselective antagonist.", "entity1": "GM-CSF", "entity2": "timolol", "span1": [38, 44], "span2": [138, 145]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6068": {"label": 3, "data": {"text": "The protein kinase C inhibitor (+)-1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) abolished the effects of phorbol esters and NE and decreased basal mRNA levels by 52 +/- 3%.", "entity1": "protein kinase C", "entity2": "(+)-1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride", "span1": [4, 20], "span2": [31, 96]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10587": {"label": 5, "data": {"text": "BACKGROUND: To assess the sensitivity of biochemical, physiological, and pharmacological markers of peripheral norepinephrine (NE) transporter (NET) function, we chronically antagonized NET by a range of doses of duloxetine [(+)-N-methyl-3-(1-naphthalenyloxy)-2 thiophenepropanamine], which blocks the NE reuptake process.", "entity1": "NET", "entity2": "(+)-N-methyl-3-(1-naphthalenyloxy)-2 thiophenepropanamine", "span1": [186, 189], "span2": [225, 282]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"4913": {"label": 1, "data": {"text": "In the in vitro assay, kinsenoside (20 and 50\u03bcg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system.", "entity1": "CAT", "entity2": "glucose", "span1": [203, 206], "span2": [276, 283]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10168": {"label": 1, "data": {"text": "Thus we have shown that low-dose theophylline exerts an anti-asthma effect through increasing activation of HDAC which is subsequently recruited by corticosteroids to suppress inflammatory genes.", "entity1": "HDAC", "entity2": "corticosteroids", "span1": [108, 112], "span2": [148, 163]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6104": {"label": 8, "data": {"text": "Voltage-clamp data combined with NE uptake data from these same cells indicate that hNETs have two functional modes of conduction: a classical transporter mode (T-mode) and a novel channel mode (C-mode).", "entity1": "hNETs", "entity2": "NE", "span1": [84, 89], "span2": [33, 35]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"4922": {"label": 1, "data": {"text": "Cholesterol uptake from lipoproteins, intracellular vesicle transport and lipid transfer are also modified by oxysterols.", "entity1": "lipoproteins", "entity2": "oxysterols", "span1": [24, 36], "span2": [110, 120]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"13864": {"label": 1, "data": {"text": "OBJECTIVE: Mitiglinide, a rapid- and short-acting insulinotropic sulfonylurea receptor ligand, exhibits hypoglycemic action unlike other sulfonylureas.", "entity1": "sulfonylurea receptor", "entity2": "sulfonylureas", "span1": [65, 86], "span2": [137, 150]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3697": {"label": 3, "data": {"text": "Tolbutamide and gliclazide block the K(ATP) channel K(ir)6.2/Sur1, causing membrane depolarization and stimulating insulin secretion in pancreatic beta cells.", "entity1": "K(ir)6.2", "entity2": "Tolbutamide", "span1": [52, 60], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4720": {"label": 3, "data": {"text": "In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of TCDD on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "entity1": "Lef1", "entity2": "TCDD", "span1": [388, 392], "span2": [241, 245]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, 3, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"15833": {"label": 1, "data": {"text": "The expression of ABCA1 and ABCG1 was induced by 24-OHC, as well as TO901317 and retinoic acid, which are ligands of the nuclear receptors LXR/RXR.", "entity1": "nuclear receptors", "entity2": "retinoic acid", "span1": [121, 138], "span2": [81, 94]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"619": {"label": 3, "data": {"text": "Taken together, these data demonstrated that PLA2 inhibitors BPB and AACOCF3 are robust inhibitors of IL-2 expression at both the mRNA and protein levels in murine splenocytes.", "entity1": "IL-2", "entity2": "BPB", "span1": [102, 106], "span2": [61, 64]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8076": {"label": 3, "data": {"text": "This study was designed to test the hypothesis that orlistat inhibits CESs with higher potency toward CES1 than CES2, a carboxylesterase with little lipase activity.", "entity1": "CES1", "entity2": "orlistat", "span1": [102, 106], "span2": [52, 60]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15559": {"label": 1, "data": {"text": "Taken together, our data demonstrate that puerarin attenuates MPTP-induced dopaminergic neuronal degeneration via modulating GDNF expression, PI3K/Akt pathway and GSH activation, which subsequently ameliorate MPTP-induced ROS formation and decrease of Lamp 2A expression.", "entity1": "PI3K", "entity2": "puerarin", "span1": [142, 146], "span2": [42, 50]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10687": {"label": 3, "data": {"text": "Ex vivo, lumiracoxib inhibited COX-1-derived thromboxane B(2) (TxB(2)) generation with an ID(50) of 33 mg kg(-1), whereas COX-2-derived production of prostaglandin E(2) (PGE(2)) in the lipopolysaccharide-stimulated rat air pouch was inhibited with an ID(50) value of 0.24 mg kg(-1).", "entity1": "COX-1", "entity2": "lumiracoxib", "span1": [31, 36], "span2": [9, 20]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"12377": {"label": 1, "data": {"text": "Methods: Cocktail approach was used to evaluate the influence of IR and IPC on the activities of CYP1A2, CYP2C9, CYP2E1, CYP2D6 and CYP3A4, which were reflected by the changes of pharmacokinetic parameters of five specific probe drugs: caffeine, chlorzoxazone, tolbutamide, metoprolol and midazolam, respectively.", "entity1": "CYP1A2", "entity2": "caffeine", "span1": [97, 103], "span2": [236, 244]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"299": {"label": 1, "data": {"text": "The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM).", "entity1": "5-HT1A", "entity2": "(+/-)-pindolol", "span1": [340, 346], "span2": [372, 386]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"5788": {"label": 9, "data": {"text": "A cDNA encoding the complete amino acid sequence of aminoacylase 1 (N-acylamino acid aminohydrolase, ACY-1) [EC 3.5.1.14], a dimeric metalloprotein having two Zn2+ in the molecule, which catalyzes the deacylation of N-acylated L-amino acids except L-aspartic acid, has been isolated from porcine kidney lambda gt10 cDNA library and sequenced.", "entity1": "aminoacylase 1", "entity2": "L-aspartic acid", "span1": [52, 66], "span2": [248, 263]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"4013": {"label": 3, "data": {"text": "Compared with the untreated colitis group, the curcumin-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-\u03baB mRNA, IL-27 mRNA, TLR4 protein, NF-\u03baB p65 protein, and IL-27 p28 protein (p < 0.05).", "entity1": "IL-27", "entity2": "curcumin", "span1": [285, 290], "span2": [47, 55]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11545": {"label": 3, "data": {"text": "Dexamethasone suppresses histamine synthesis by repressing both transcription and activity of HDC in allergic rats.", "entity1": "HDC", "entity2": "Dexamethasone", "span1": [94, 97], "span2": [0, 13]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1276": {"label": 7, "data": {"text": "Ever since the discovery that (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) is a cofactor of NOS, its function has been the object of intense research and occasional controversy.", "entity1": "NOS", "entity2": "BH4", "span1": [89, 92], "span2": [67, 70]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 7, -1, -1, -1, -1, -1, -1]},
	"37": {"label": 1, "data": {"text": "Adrenaline via alpha 2-adrenoceptors inhibited the Ca2+ currents by about 50%.", "entity1": "alpha 2-adrenoceptors", "entity2": "Adrenaline", "span1": [15, 36], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13265": {"label": 9, "data": {"text": "CONCLUSION: In postmenopausal women, isolated isoflavone treatment does not affect ABCA1-dependent cholesterol efflux potential from macrophages but increases circulating pre-beta high-density lipoprotein level, which could provide beneficial vascular effects.", "entity1": "ABCA1", "entity2": "isoflavone", "span1": [83, 88], "span2": [46, 56]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"11087": {"label": 1, "data": {"text": "Loperamide, an opiate analog, differently modifies the adrenocorticotropin responses to corticotropin-releasing hormone and lysine vasopressin in patients with Addison's disease.", "entity1": "adrenocorticotropin", "entity2": "Loperamide", "span1": [55, 74], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8167": {"label": 1, "data": {"text": "To determine how pol \u03b2 discriminates between anti- and syn-8-oxoG, we introduced a point mutation (R283K) to alter insertion specificity.", "entity1": "pol \u03b2", "entity2": "anti- and syn-8-oxoG", "span1": [17, 22], "span2": [45, 65]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1647": {"label": 3, "data": {"text": "These results suggest that clomipramine induces hyperglycemia in mice by blocking the 5-HT(2B )and/or 5-HT(2C) receptors, which results in facilitation of adrenaline release.", "entity1": "5-HT(2B )", "entity2": "clomipramine", "span1": [86, 95], "span2": [27, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9379": {"label": 1, "data": {"text": "However, recovery from modulation by cyclothiazide was twofold slower for GluR-AiBi than for homomeric GluR-Ai, indicating that the GluR-A and GluR-B subunits are not functionally equivalent in controlling sensitivity to cyclothiazide.", "entity1": "GluR-B", "entity2": "cyclothiazide", "span1": [143, 149], "span2": [221, 234]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, 9]},
	"4459": {"label": 2, "data": {"text": "However, after 12h CdCl2 treatment, cell viability diminished in 50%, accompanied by a drastic decrease of metallothionein-II production, and an increase in p53 activation and the pro-apoptotic protein Bax.", "entity1": "Bax", "entity2": "CdCl2", "span1": [202, 205], "span2": [19, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"14792": {"label": 2, "data": {"text": "Human immortalized corneal fibroblasts were treated with TGF-\u03b2 in the presence of TSA, the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI), the antioxidant N-acetyl-cysteine (NAC), the NF-E2-related factor 2-antioxidant response element (Nrf2-ARE) activator sulforaphane, or small interfering RNA.", "entity1": "ARE", "entity2": "sulforaphane", "span1": [247, 250], "span2": [262, 274]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2700": {"label": 2, "data": {"text": "Improvements from baseline in mean glycosylated haemoglobin (HbA(1c)) were significantly greater with sitagliptin monotherapy than with placebo in patients with type 2 diabetes.", "entity1": "HbA(1c)", "entity2": "sitagliptin", "span1": [61, 68], "span2": [102, 113]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7374": {"label": 1, "data": {"text": "Histamine regulates many functions by binding to four histamine G-coupled receptor proteins (H1R, H2R, H3R and H4R).", "entity1": "H4R", "entity2": "Histamine", "span1": [111, 114], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2730": {"label": 3, "data": {"text": "Indomethacin and SC-236, a selective cyclooxygenase-2 (COX-2) inhibitor, exerted a similar effect as sulindac.", "entity1": "COX-2", "entity2": "SC-236", "span1": [55, 60], "span2": [17, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5340": {"label": 1, "data": {"text": "S1P activated phosphatidylinositol 3-kinase (PI3K)/Akt signaling, leading to the inhibition of glycogen synthase kinase-3\u03b2 and the nuclear translocation of \u03b2-catenin, followed by the increase of the transcriptional activity by \u03b2-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells.", "entity1": "\u03b2-catenin", "entity2": "S1P", "span1": [156, 165], "span2": [0, 3]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9889": {"label": 1, "data": {"text": "Both radioligands labeled mAch receptors in these brain regions, and the relative regional distributions of the specific binding of 3H-NMPB in vivo paralleled the distribution of mAch receptors.", "entity1": "mAch receptors", "entity2": "3H-NMPB", "span1": [179, 193], "span2": [132, 139]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12512": {"label": 9, "data": {"text": "Carvedilol had no effect on the pressor response elicited by angiotensin II, indicating a lack of nonspecific vasodilator activity.", "entity1": "angiotensin II", "entity2": "Carvedilol", "span1": [61, 75], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8098": {"label": 2, "data": {"text": "These results suggested that wogonin could inhibit H2O2-induced vascular permeability by downregulating the phosphorylation of cav-1, and that it might have a therapeutic potential for the diseases associated with the development of both oxidant and vascular permeability.", "entity1": "cav-1", "entity2": "H2O2", "span1": [127, 132], "span2": [51, 55]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2710": {"label": 2, "data": {"text": "There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the parathion-treated cells.", "entity1": "Rac-3", "entity2": "parathion", "span1": [50, 55], "span2": [140, 149]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"391": {"label": 1, "data": {"text": "The e2 domain thus plays some role in CP 55,940 binding but none in SR 141716A recognition, binding of the latter clearly implicating residues in the adjoining transmembrane helices.", "entity1": "e2 domain", "entity2": "CP 55,940", "span1": [4, 13], "span2": [38, 47]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12482": {"label": 8, "data": {"text": "Cynomolgus FMO1, FMO2, FMO3, and FMO5 metabolized benzydamine, and FMO1/FMO3 and FMO3 also metabolized methimazole and trimethylamine, respectively.", "entity1": "FMO1", "entity2": "methimazole", "span1": [67, 71], "span2": [103, 114]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4580": {"label": 3, "data": {"text": "Levels of Cx43 protein were also decreased in a dose- and time-dependent manner following antofine treatment.", "entity1": "Cx43", "entity2": "antofine", "span1": [10, 14], "span2": [90, 98]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2629": {"label": 3, "data": {"text": "We show that sorafenib (BAY 43-9006, Nexavar) potently inhibits FLT3 enzymatic and signaling activities.", "entity1": "FLT3", "entity2": "Nexavar", "span1": [64, 68], "span2": [37, 44]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14096": {"label": 1, "data": {"text": "Our studies demonstrate that thalidomide, lenalidomide and another immunomodulatory drug, pomalidomide, bound endogenous CRBN and recombinant CRBN-DNA damage binding protein-1 (DDB1) complexes.", "entity1": "DNA damage binding protein-1", "entity2": "thalidomide", "span1": [147, 175], "span2": [29, 40]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, 9]},
	"6219": {"label": 3, "data": {"text": "This study thus demonstrates that the first administration of the recommended starting dose of irbesartan induces a greater and longer lasting Ang II receptor blockade than that of valsartan and losartan in normotensive subjects.", "entity1": "Ang II receptor", "entity2": "valsartan", "span1": [143, 158], "span2": [181, 190]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"960": {"label": 5, "data": {"text": "In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the alpha(2)-autoreceptors, sharing this property with rauwolscine, phentolamine, and idazoxan.", "entity1": "alpha(2)-autoreceptors", "entity2": "phentolamine", "span1": [155, 177], "span2": [219, 231]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12380": {"label": 1, "data": {"text": "Methods: Cocktail approach was used to evaluate the influence of IR and IPC on the activities of CYP1A2, CYP2C9, CYP2E1, CYP2D6 and CYP3A4, which were reflected by the changes of pharmacokinetic parameters of five specific probe drugs: caffeine, chlorzoxazone, tolbutamide, metoprolol and midazolam, respectively.", "entity1": "CYP2D6", "entity2": "metoprolol", "span1": [121, 127], "span2": [274, 284]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3308": {"label": 1, "data": {"text": "Steady-state fluorescence was utilized to assess Ca(2+) affinity in isolated cardiac (c)TnCs containing F27W and did not necessarily mirror the fiber Ca(2+) sensitivity.", "entity1": "cardiac (c)TnCs", "entity2": "Ca(2+)", "span1": [77, 92], "span2": [150, 156]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"12326": {"label": 2, "data": {"text": "It was reported previously that FVII gene (F7) expression was up-regulated by ribavirin treatment in hepatitis C virus-infected haemophilia patients; however, its precise mechanism is still unknown.", "entity1": "F7", "entity2": "ribavirin", "span1": [43, 45], "span2": [78, 87]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2499": {"label": 3, "data": {"text": "Licofelone almost abolished 5-LOX activity by inhibiting leukotriene B4 generation in rabbit neutrophils and prevented platelet thromboxane B2 production from whole blood.", "entity1": "5-LOX", "entity2": "Licofelone", "span1": [28, 33], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"10880": {"label": 3, "data": {"text": "Irinotecan (CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) has exhibited clinical activities against a broad spectrum of carcinomas by inhibiting DNA topoisomerase I (Topo I).", "entity1": "Topo I", "entity2": "Irinotecan", "span1": [196, 202], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7968": {"label": 1, "data": {"text": "We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.", "entity1": "insulin", "entity2": "Orlistat", "span1": [212, 219], "span2": [58, 66]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5556": {"label": 2, "data": {"text": "Treatment of cells with BCNU to inhibit glutathione reductase (GR) enhanced the CpG-induced intracellular oxidation and decreased the GSH/GSSG, with increased activation of NF-kappaB and a doubling in the CpG-induced production of IL-6 and TNF-alpha.", "entity1": "IL-6", "entity2": "BCNU", "span1": [231, 235], "span2": [24, 28]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, 2, -1, -1, -1, 3, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"13268": {"label": 1, "data": {"text": "We studied in a clinical trial whether isolated isoflavone treatment in postmenopausal women could affect reverse cholesterol transport as evaluated by adenosine triphosphate-binding cassette A1- (ABCA1), dependent cholesterol efflux from macrophages.", "entity1": "ABCA1", "entity2": "isoflavone", "span1": [197, 202], "span2": [48, 58]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"795": {"label": 1, "data": {"text": "Additionally, experiments with the non-desensitizing site-directed mutant GluR3(L507Y) (Stern-Bach, Y., Russo, S., Neuman, M. and Rosenmund, C., A point mutation in the glutamate binding site blocks desensitization of AMPAAMPA receptors.", "entity1": "AMPA receptors", "entity2": "AMPA", "span1": [222, 236], "span2": [218, 222]}, "weak_labels": [-1, -1, 0, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8807": {"label": 8, "data": {"text": "Rates of benzydamine N-oxygenation (catalyzed by FMO3) varied (approximately 20-fold) among the 28 cynomolgus livers and were significantly correlated with FMO3 protein expression, indicating that the inter-animal variations in benzydamine N-oxygenation might be partly accounted for by the variable FMO3 expression.", "entity1": "FMO3", "entity2": "N", "span1": [300, 304], "span2": [240, 241]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"16056": {"label": 3, "data": {"text": "Simvastatin and lovastatin metabolized through CYP3A have the highest potency for drug-drug interaction with potent CYP3A inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the hepatitis C virus (HCV) PI, telaprevir or boceprevir, and therefore their coadministration is contraindicated.", "entity1": "CYP3A", "entity2": "cobicistat", "span1": [116, 121], "span2": [155, 165]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6174": {"label": 1, "data": {"text": "Based on these results, we conclude that the NSAIDs ibuprofen and salicylic acid inhibit cAMP-mediated Cl- secretion in human colonic and airway epithelia via a direct inhibition of CFTR Cl- channels as well as basolateral membrane K+ channels.", "entity1": "Cl- channels", "entity2": "cAMP", "span1": [187, 199], "span2": [89, 93]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"267": {"label": 0, "data": {"text": "Drosophila GABA-gated chloride channel: modified [3H]EBOB binding site associated with Ala-->Ser or Gly mutants of Rdl subunit.", "entity1": "Rdl", "entity2": "Gly", "span1": [115, 118], "span2": [100, 103]}, "weak_labels": [-1, -1, 0, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"132": {"label": 3, "data": {"text": "Felodipine and the p-chloro analogue inhibited the basal (Ca2+/calmodulin-independent) activity of cAMP phosphodiesterase as well as the calmodulin-stimulated activity.", "entity1": "calmodulin", "entity2": "Felodipine", "span1": [137, 147], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13091": {"label": 2, "data": {"text": "The most active of these compounds, gliquidone, is shown to be as potent as pioglitazone at inducing PPARgamma target gene expression.", "entity1": "PPARgamma", "entity2": "gliquidone", "span1": [101, 110], "span2": [36, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7009": {"label": 3, "data": {"text": "Significant advances in the treatment of clear-cell RCC have been derived from agents that target these pathways, including the multiple-kinase inhibitors (MKIs) sorafenib, sunitinib, and AG013736, which target multiple VEGFRs as well as PDGFR-beta.", "entity1": "kinase", "entity2": "AG013736", "span1": [137, 143], "span2": [188, 196]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"16022": {"label": 1, "data": {"text": "Haloperidol promotes mTORC1-dependent phosphorylation of ribosomal protein S6 via dopamine- and cAMP-regulated phosphoprotein of 32 kDa and inhibition of protein phosphatase-1.", "entity1": "dopamine- and cAMP-regulated phosphoprotein of 32 kDa", "entity2": "Haloperidol", "span1": [82, 135], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9846": {"label": 8, "data": {"text": "gamma-Butyrobetaine hydroxylase catalyse the last step in carnitine biosynthesis, the formation of L-carnitine from gamma-butyrobetaine, a reaction dependent on Fe2+, alpha-ketoglutarate, ascorbate and oxygen.", "entity1": "gamma-Butyrobetaine hydroxylase", "entity2": "L-carnitine", "span1": [0, 31], "span2": [99, 110]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"12584": {"label": 1, "data": {"text": "Coexpression of the flip and flop splice variants of GluR-A, in the absence of GluR-B, revealed that heteromeric AMPA receptors with intermediate sensitivity to cyclothiazide, similar to responses observed for the combinations GluR-AoBi or GluR-AiBo, could be generated independently of the presence of the GluR-B subunit.", "entity1": "GluR-A", "entity2": "cyclothiazide", "span1": [53, 59], "span2": [161, 174]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7480": {"label": 1, "data": {"text": "This effect probably involves interaction of phenserine with a regulatory element in the 5'-untranslated region of the APP gene that controls APP expression.", "entity1": "APP", "entity2": "phenserine", "span1": [119, 122], "span2": [45, 55]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6249": {"label": 1, "data": {"text": "Eletriptan, like sumatriptan, zolmitriptan, naratriptan and rizatriptan had highest affinity for the human 5-HT1B, 5-HT1D and putative 5-ht1f receptor.", "entity1": "5-ht1f", "entity2": "zolmitriptan", "span1": [135, 141], "span2": [30, 42]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8086": {"label": 2, "data": {"text": "We identified one compound, E235 (N-(1-benzyl-piperidin-4-yl)-2-(4-fluoro-phenyl)-benzo[d]imidazo[2,1-b]thiazole-7-carboxamide), that activated the ISR and dose-dependently increased levels of ATF4 in transformed cells.", "entity1": "ATF4", "entity2": "(N-(1-benzyl-piperidin-4-yl)-2-(4-fluoro-phenyl)-benzo[d]imidazo[2,1-b]thiazole-7-carboxamide)", "span1": [193, 197], "span2": [33, 127]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12034": {"label": 8, "data": {"text": "Compound I of the peroxidases is represented as EO, and oxidation of I- by EO is postulated to form enzyme-bound hypoiodite, represented in our scheme as [EOI]-.", "entity1": "EO", "entity2": "hypoiodite", "span1": [48, 50], "span2": [113, 123]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15768": {"label": 1, "data": {"text": "Furthermore, we detected that ICI treatment induced glycogen synthase kinase (Gsk3-\u03b2) Ser 9 phosphorylation, which correlates with cyclin D1 nuclear localization.", "entity1": "cyclin D1", "entity2": "ICI", "span1": [131, 140], "span2": [30, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6899": {"label": 1, "data": {"text": "In vitro studies demonstrated that the retinoid X receptor (RXR) retinoid, bexarotene, at biologically relevant concentrations of 10(-6) M to 10(-8) M, upregulated both the p55 and p75 subunits of the IL-2R and enhanced 5- to 10-fold the susceptibility of T-cell leukemia cells to denileukin diftitox.", "entity1": "retinoid X receptor", "entity2": "bexarotene", "span1": [39, 58], "span2": [75, 85]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7361": {"label": 4, "data": {"text": "Moreover, ERalpha mediated the protection afforded by estrogen since only the ERalpha agonist, HPTE, but not the ERbeta agonist, DPN, protected against dopamine cell loss.", "entity1": "ERbeta", "entity2": "DPN", "span1": [113, 119], "span2": [129, 132]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"5859": {"label": 5, "data": {"text": "A number of selective 5-HT3 antagonists have been developed including ondansetron, granisetron, tropisetron renzapride and zacopride.", "entity1": "5-HT3", "entity2": "tropisetron", "span1": [22, 27], "span2": [96, 107]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3729": {"label": 3, "data": {"text": "The present results indicated that N-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways.", "entity1": "Ras", "entity2": "BPs", "span1": [224, 227], "span2": [37, 40]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2236": {"label": 3, "data": {"text": "Additionally, dasatinib leads to growth inhibition of a KITD816V-harboring human masto-cytosis cell line.", "entity1": "D816V", "entity2": "dasatinib", "span1": [59, 64], "span2": [14, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"846": {"label": 3, "data": {"text": "Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial.", "entity1": "cyclooxygenase 2", "entity2": "rofecoxib", "span1": [41, 57], "span2": [28, 37]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8256": {"label": 2, "data": {"text": "In\u00a0vitro molecular pharmacology studies showed that 5-HT2C agonists potent for attenuating the DOI-elicited-HTR also reduced the efficacy of DOI to activate mouse 5-HT2C receptor-mediated PLC signaling in HEK cells.", "entity1": "mouse 5-HT2C", "entity2": "DOI", "span1": [157, 169], "span2": [141, 144]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11483": {"label": 1, "data": {"text": "CONCLUSIONS: Ketorolac is relatively COX-1 selective while bromfenac is potently selective for COX-2 over COX-1.", "entity1": "COX-2", "entity2": "bromfenac", "span1": [95, 100], "span2": [59, 68]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5236": {"label": 2, "data": {"text": "To confirm this novel mechanism of bleomycin-induced fibrogenesis, we attempted to upregulate Nrf2 and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance.", "entity1": "Nrf2", "entity2": "bleomycin", "span1": [94, 98], "span2": [35, 44]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7546": {"label": 3, "data": {"text": "Phenelzine (PLZ), a nonselective irreversible inhibitor of monoamine oxidase (MAO), also inhibits GABA-transaminase (GABA-T), markedly increasing brain GABA levels.", "entity1": "monoamine oxidase", "entity2": "PLZ", "span1": [59, 76], "span2": [12, 15]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6090": {"label": 2, "data": {"text": "Amantadine (1-aminoadamantane) induced Fos expression in the central, dorsal-medial and ventral-medial part of the striatum.", "entity1": "Fos", "entity2": "Amantadine", "span1": [39, 42], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6675": {"label": 3, "data": {"text": "Furthermore, RT-PCR analyses revealed that minocycline treatment increased expression of interleukin-10 mRNA but decreased tumor necrosis factor-alpha expression.", "entity1": "tumor necrosis factor-alpha", "entity2": "minocycline", "span1": [123, 150], "span2": [43, 54]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13425": {"label": 1, "data": {"text": "D-glucose stimulation of L-arginine transport and nitric oxide synthesis results from activation of mitogen-activated protein kinases p42/44 and Smad2 requiring functional type II TGF-beta receptors in human umbilical vein endothelium.", "entity1": "type II TGF-beta receptors", "entity2": "D-glucose", "span1": [172, 198], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"1347": {"label": 1, "data": {"text": "Several active analogues were also evaluated for their ability to block uptake of DA, 5-HT, and NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-hNET cells.", "entity1": "hNET", "entity2": "[(125)I] RTI-55", "span1": [170, 174], "span2": [122, 137]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15415": {"label": 1, "data": {"text": "This study evaluates the production of inflammatory biomarkers (IL-1\u03b2, IL-8, IL-10, TNF\u03b1) and the influence of gene expression transporters and enzymes related to cholesterol absorption and metabolism (NPC1L1, ABCG5/8, HMGCoA, ACAT) produced by 7-ketosterols (stigmasterol/cholesterol) in Caco-2 cells.", "entity1": "IL-1\u03b2", "entity2": "cholesterol", "span1": [64, 69], "span2": [273, 284]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 8, -1, -1]},
	"3380": {"label": 6, "data": {"text": "Benzodiazepines (BDZs) depress neuronal excitability via positive allosteric modulation of inhibitory GABA(A) receptors (GABA(A)R).", "entity1": "GABA(A) receptors", "entity2": "BDZs", "span1": [102, 119], "span2": [17, 21]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, 6, 6, -1, -1, -1, -1, -1, -1, -1]},
	"5008": {"label": 1, "data": {"text": "Five classes of chalcogenopyrylium dyes (CGPs) were examined for their ability to modulate transport of [(3)H]estradiol glucuronide (E217\u03b2G) (a prototypical MRP substrate) into MRP-enriched inside-out membrane vesicles.", "entity1": "MRP", "entity2": "chalcogenopyrylium", "span1": [157, 160], "span2": [16, 34]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, 8, 8, -1, -1, -1, -1]},
	"8493": {"label": 3, "data": {"text": "AlCl3 markedly reduced AA performance and activities of cytochrome c oxidase (COX) and acetylcholinesterase (AChE) in all regions.", "entity1": "cytochrome c oxidase", "entity2": "AlCl3", "span1": [56, 76], "span2": [0, 5]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13838": {"label": 8, "data": {"text": "Mammalian glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of l-glutamate to 2-oxoglutarate using NAD(P)(+) as coenzyme.", "entity1": "GDH", "entity2": "2-oxoglutarate", "span1": [35, 38], "span2": [136, 150]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"6856": {"label": 1, "data": {"text": "Bosentan partially prevented stress-induced both hyperglycemia and decrease in glycogen content while it completely blocked the stress-induced decrease in insulin level in normoglycemic stressed rats.", "entity1": "insulin", "entity2": "Bosentan", "span1": [155, 162], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14000": {"label": 3, "data": {"text": "Cabozantinib (XL184) is a small-molecule kinase inhibitor with potent activity toward MET and VEGF receptor 2 (VEGFR2), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including RET, KIT, AXL, and FLT3.", "entity1": "AXL", "entity2": "Cabozantinib", "span1": [249, 252], "span2": [0, 12]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8046": {"label": 3, "data": {"text": "Exposure of H9c2 cells to high glucose reduced AMPK activity, inhibited Jun NH2-terminal kinase 1 (JNK1)-B-cell lymphoma 2 (Bcl-2) signaling, and promoted Beclin1 binding to Bcl-2.", "entity1": "B-cell lymphoma 2", "entity2": "glucose", "span1": [105, 122], "span2": [31, 38]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3479": {"label": 0, "data": {"text": "Uncoupling from this channel was achieved by co-expression of an mGluR1 C-terminal protein designed to disrupt a previously described direct interaction between these two proteins, suggesting that this interaction allows incorporation of Ca(V2.1) into the mGluR1/Homer signaling complex, thereby preserving modulation in the presence of scaffolding Homer proteins.", "entity1": "mGluR1", "entity2": "C", "span1": [65, 71], "span2": [72, 73]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14700": {"label": 3, "data": {"text": "The presence of steroid hormones most probably causes the degradation of the Tat2 permease and impairment of tryptophan import.", "entity1": "Tat2", "entity2": "steroid", "span1": [77, 81], "span2": [16, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1411": {"label": 1, "data": {"text": "RATIONALE: There is substantial evidence that lisuride can produce effects linked to 5-HT(1A) receptor occupancy.", "entity1": "5-HT(1A)", "entity2": "lisuride", "span1": [85, 93], "span2": [46, 54]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"6569": {"label": 3, "data": {"text": "Mutants Y751A, D950A, and F1004A had reduced sensitivity to milrinone (K(i) changed from 0.66 microM for the recombinant PDE3A to 7.5 to 156 microM for the mutants), and diminished sensitivity to cilostazol (K(i) of the mutants were 18- to 371-fold higher than that of the recombinant PDE3A).", "entity1": "F1004A", "entity2": "milrinone", "span1": [26, 32], "span2": [60, 69]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4432": {"label": 8, "data": {"text": "Type 2 11\u03b2-hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.", "entity1": "HSD11B2", "entity2": "cortisone", "span1": [55, 62], "span2": [98, 107]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1]},
	"15672": {"label": 1, "data": {"text": "Native GLP-1 stimulates insulin secretion in a glucose-dependent manner, as well as suppressing glucagon production and slowing gastric emptying.", "entity1": "insulin", "entity2": "glucose", "span1": [24, 31], "span2": [47, 54]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"4242": {"label": 8, "data": {"text": "As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and xanthine oxidase was identified as the likely source of TES-stimulated superoxide production.", "entity1": "xanthine oxidase", "entity2": "TES", "span1": [115, 131], "span2": [171, 174]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"6660": {"label": 3, "data": {"text": "Patients stable on warfarin therapy and concurrently taking a cyclooxygenase-2 (COX-2) inhibitor comparator (traditional nonsteroidal antiinflammatory medications, salsalate, or acetaminophen) randomly received celecoxib 200 mg/day or rofecoxib 25 mg/day for three weeks.", "entity1": "cyclooxygenase-2", "entity2": "celecoxib", "span1": [62, 78], "span2": [211, 220]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9853": {"label": 1, "data": {"text": "Salicylates inhibit (125)I-ET-1 binding to recombinant rat ETA receptors.", "entity1": "rat ETA receptors", "entity2": "Salicylates", "span1": [55, 72], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1808": {"label": 3, "data": {"text": "In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit human Na(V)1.5 sodium channels expressed in Chinese Hamster Ovary (CHO-K1) cells.", "entity1": "human Na(V)1.5", "entity2": "alpha-hydroxyphenylamide", "span1": [135, 149], "span2": [41, 65]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13796": {"label": 3, "data": {"text": "The most successful example of kinase blockers is Imatinib (Imatinib mesylate, Gleevec, STI571), the inhibitor of Bcr/Abl oncoprotein, which has become a first-line therapy for chronic myelogenous leukemia.", "entity1": "Bcr", "entity2": "Imatinib", "span1": [114, 117], "span2": [50, 58]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10235": {"label": 8, "data": {"text": "During polyamine catabolism, spermine and spermidine are first acetylated by spermidine/spermine N(1)-acetyltransferase (SSAT) and subsequently oxidized by polyamine oxidase (PAO) to produce spermidine and putrescine, respectively.", "entity1": "polyamine oxidase", "entity2": "spermidine", "span1": [156, 173], "span2": [191, 201]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"3118": {"label": 8, "data": {"text": "First, addition of apolipoprotein A-I (apoA-I), a direct acceptor of the ATP-binding cassette transporter A1 (ABCA1)-secreted lipids, increased alpha-tocopherol secretion in a dose-dependent manner.", "entity1": "ATP-binding cassette transporter A1", "entity2": "alpha-tocopherol", "span1": [73, 108], "span2": [144, 160]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"14471": {"label": 3, "data": {"text": "Blood pressure was increased in rats exposed to IH, and treatment with the PDK-1 inhibitor OSU-03012 [2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl}-acetamide] (33 mg/day) lowered blood pressure in IH but not sham group rats.", "entity1": "PDK-1", "entity2": "OSU-03012", "span1": [75, 80], "span2": [91, 100]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"135": {"label": 3, "data": {"text": "Calmodulin was relatively ineffective in preventing inhibition of cAMP phosphodiesterase by felodipine and the p-chloro analogue.", "entity1": "cAMP phosphodiesterase", "entity2": "felodipine", "span1": [66, 88], "span2": [92, 102]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1836": {"label": 3, "data": {"text": "The reciprocal inhibition of SR-BI and ABCA1 by BLT-4 and glyburide raises the possibility that these proteins may share similar or common steps in their mechanisms of lipid transport.", "entity1": "SR-BI", "entity2": "glyburide", "span1": [29, 34], "span2": [58, 67]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"12364": {"label": 1, "data": {"text": "Structural studies with R283K pol \u03b2 show that the binary DNA complex has 8-oxoG in equilibrium between anti- and syn-forms.", "entity1": "pol \u03b2", "entity2": "8-oxoG", "span1": [30, 35], "span2": [73, 79]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15581": {"label": 9, "data": {"text": "We rescued cells lethally depleted of endogenous Cdk1 with an exogenous Cdk1 conferring sensitivity to one ATP analogue inhibitor (1NMPP1) and resistance to another (RO3306).", "entity1": "Cdk1", "entity2": "RO3306", "span1": [72, 76], "span2": [166, 172]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"15131": {"label": 3, "data": {"text": "The fecal elimination, IC, and systemic clearance of apixaban were increased upon AC administration in both BDC rats and dogs and were decreased in BDC rats dosed with GF-120918, a dual BCRP and P-gp inhibitor).", "entity1": "BCRP", "entity2": "GF-120918", "span1": [186, 190], "span2": [168, 177]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12090": {"label": 3, "data": {"text": "or peripheral neuronal MAO by debrisoquin (40 mg/kg i.p.).", "entity1": "MAO", "entity2": "debrisoquin", "span1": [23, 26], "span2": [30, 41]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8755": {"label": 8, "data": {"text": "Kinetic analyses revealed that the affinity and clearance of UGT2B10 for amitriptyline, imipramine, and diphenhydramine are significantly higher than the corresponding values of UGT1A4 and UGT1A3, although the Vmax values of UGT1A4 toward these drugs are considerably higher.", "entity1": "UGT1A3", "entity2": "imipramine", "span1": [189, 195], "span2": [88, 98]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1057": {"label": 3, "data": {"text": "In contrast, in the presence of Ca UFH accelerated the inhibition of factor Xa by antithrombin 10-fold more efficiently than comparable concentrations of the high affinity fractions of enoxaparin and fragmin.", "entity1": "antithrombin", "entity2": "Ca", "span1": [82, 94], "span2": [32, 34]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10784": {"label": 2, "data": {"text": "The IL-18 production is located upstream of the cytokine cascade activated by simvastatin.", "entity1": "cytokine", "entity2": "simvastatin", "span1": [48, 56], "span2": [78, 89]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"6645": {"label": 1, "data": {"text": "On the other hand, ligands for the renal Na(+)-transporter (amiloride and triamterene) and for imidazoline recognition sites (guanabenz, guanfacine and agmatine) displaced the binding of [(3)H]prazosin to phentolamine-insensitive sites at micromolar concentrations.", "entity1": "Na(+)-transporter", "entity2": "triamterene", "span1": [41, 58], "span2": [74, 85]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"5970": {"label": 3, "data": {"text": "However, betaxolol produces less systemic beta 2- and possibly beta 1-adrenergic receptor blockade than either timolol or levobunolol.", "entity1": "beta 1-adrenergic receptor", "entity2": "timolol", "span1": [63, 89], "span2": [111, 118]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"14375": {"label": 3, "data": {"text": "These findings suggest that NFD inhibited the EGF-induced invasion and migration of MDA-MB-231 cells via EGFR-dependent PI3K/Akt signaling, leading to the down-regulation of MMP-9 expression.", "entity1": "Akt", "entity2": "NFD", "span1": [125, 128], "span2": [28, 31]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12561": {"label": 1, "data": {"text": "The subtypes of alpha 1-adrenoceptor mediating contractions to exogenous noradrenaline (NA) in rat aorta have been examined in both biochemical and functional studies.", "entity1": "alpha 1-adrenoceptor", "entity2": "noradrenaline", "span1": [16, 36], "span2": [73, 86]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10749": {"label": 3, "data": {"text": "Clinical studies in cancer patients treated with the new fluoropyrimidine analogue capecitabine (N4-pentoxycarbonyl-5'-5-fluorocytidine) have shown that plasma 2'-deoxyuridine was significantly elevated after 1 week of treatment, consistent with inhibition of thymidylate synthase (TS).", "entity1": "thymidylate synthase", "entity2": "N4-pentoxycarbonyl-5'-5-fluorocytidine", "span1": [260, 280], "span2": [97, 135]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11744": {"label": 0, "data": {"text": "The Ves a 1 structure, which is composed of seven \u03b1-helixes and eleven \u03b2-strands, contains the \u03b2-strand/\u025bSer/\u03b1-helix structural motif, which contains the Gly-X-Ser-X-Gly consensus sequence.", "entity1": "Ves a 1", "entity2": "Gly", "span1": [4, 11], "span2": [154, 157]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7570": {"label": 9, "data": {"text": "Administration of cevimeline hydrochloride, an M3 muscarinic receptor agonist (10 mg/kg for 7 days po), but not pilocarpine (0.3 mg/kg for 7 days po), recovered the AQP5 protein level reduced by CTD and increased the AQP1 protein level above the control one.", "entity1": "AQP5", "entity2": "pilocarpine", "span1": [165, 169], "span2": [112, 123]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"12239": {"label": 8, "data": {"text": "The carboxylation of glutamic acid residues to gamma-carboxyglutamic acid (Gla) by the vitamin K-dependent gamma-glutamyl carboxylase (gamma-carboxylase) is an essential posttranslational modification required for the biological activity of a number of proteins, including proteins involved in blood coagulation and its regulation.", "entity1": "vitamin K-dependent gamma-glutamyl carboxylase", "entity2": "gamma-carboxyglutamic acid", "span1": [87, 133], "span2": [47, 73]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4187": {"label": 1, "data": {"text": "PTE, used in combination with a known JAK2/STAT3 inhibitor, AG490, further decreased the viability of osteosarcoma cells.", "entity1": "JAK2", "entity2": "PTE", "span1": [38, 42], "span2": [0, 3]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10829": {"label": 9, "data": {"text": "The reported mechanism of imatinib resistance in GISTs involves missense mutation in the kinase domain of KIT, including Thr670Ile, Tyr823Asp, and Val654Ala.", "entity1": "Thr670Ile", "entity2": "imatinib", "span1": [121, 130], "span2": [26, 34]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"739": {"label": 1, "data": {"text": "Preclinically, venlafaxine has been shown to potently inhibit dorsal raphe neuronal (DRN) firing through a 5-HT1A mediated mechanism, in a similar manner to SSRIs.", "entity1": "5-HT1A", "entity2": "venlafaxine", "span1": [107, 113], "span2": [15, 26]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12182": {"label": 2, "data": {"text": "Hence, re-expression of the p75NTR appears to partially reverse de-differentiation of prostate cancer cells by up-regulating the expression of CRABPI for localized sequestration of retinoids that are available to newly up-regulated RAR-beta, RXR-alpha, and RXR-beta.", "entity1": "CRABPI", "entity2": "retinoids", "span1": [143, 149], "span2": [181, 190]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1668": {"label": 1, "data": {"text": "In membranes from HEK293 cells transfected with alpha2-receptors, etomidate inhibited binding of the alpha2-antagonist, [3H]RX821002, with higher potency from alpha2B- and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm).", "entity1": "alpha2B- and alpha2C-receptors", "entity2": "etomidate", "span1": [159, 189], "span2": [66, 75]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10127": {"label": 1, "data": {"text": "Accordingly, docking of different COX inhibitors, including selective and non-selective ligands: rofecoxib, ketoprofen, suprofen, carprofen, zomepirac, indomethacin, diclofenac and meclofenamic acid were undertaken using the AMBER program.", "entity1": "COX", "entity2": "diclofenac", "span1": [34, 37], "span2": [166, 176]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8760": {"label": 8, "data": {"text": "Kinetic analyses revealed that the affinity and clearance of UGT2B10 for amitriptyline, imipramine, and diphenhydramine are significantly higher than the corresponding values of UGT1A4 and UGT1A3, although the Vmax values of UGT1A4 toward these drugs are considerably higher.", "entity1": "UGT1A4", "entity2": "diphenhydramine", "span1": [225, 231], "span2": [104, 119]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13669": {"label": 3, "data": {"text": "This overview focuses on the indirect antithrombin dependent pentasaccharide derivatives of idraparinux and on the most advanced oral direct inhibitors to factor Xa (rivaroxaban and apixaban) and IIa (dabigatran).", "entity1": "factor Xa", "entity2": "apixaban", "span1": [155, 164], "span2": [182, 190]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13310": {"label": 3, "data": {"text": "INTERPRETATION AND CONCLUSIONS: These results warrant further clinical studies of sorafenib for the treatment of myeloid malignancies expressing activated forms of PDGFRbeta and FLT3.", "entity1": "PDGFRbeta", "entity2": "sorafenib", "span1": [164, 173], "span2": [82, 91]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15409": {"label": 1, "data": {"text": "This study evaluates the production of inflammatory biomarkers (IL-1\u03b2, IL-8, IL-10, TNF\u03b1) and the influence of gene expression transporters and enzymes related to cholesterol absorption and metabolism (NPC1L1, ABCG5/8, HMGCoA, ACAT) produced by 7-ketosterols (stigmasterol/cholesterol) in Caco-2 cells.", "entity1": "IL-10", "entity2": "stigmasterol", "span1": [77, 82], "span2": [260, 272]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 8, -1, -1]},
	"11765": {"label": 0, "data": {"text": "The CBC physically associates with these complexes to recruit them during transcription and mediates phosphorylation at Ser-2 of the C-terminal domain (CTD) of RNA polymerase II.", "entity1": "RNA polymerase II", "entity2": "Ser", "span1": [160, 177], "span2": [120, 123]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"16017": {"label": 5, "data": {"text": "The involvement of the various DA receptor subtypes in the motor effects of N/OFQ and NOP receptor antagonists was evaluated pharmacologically, using D1/D5 (SCH23390), D2/D3 (raclopride, amisulpride) and D3 (S33084) receptor antagonists, and by using D2 receptor knockout mice.", "entity1": "D2", "entity2": "amisulpride", "span1": [168, 170], "span2": [187, 198]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15691": {"label": 1, "data": {"text": "Conclusion The results of this work contribute information regarding the antinociceptive properties of CAT on acute pain and show that, at least in part, TRPV1, TRPM8, ASIC, glutamate receptors, PKC and PKA participate in CAT's antinociceptive mechanism.", "entity1": "TRPV1", "entity2": "CAT", "span1": [154, 159], "span2": [222, 225]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"97": {"label": 3, "data": {"text": "Catecholamines (adrenaline, noradrenaline and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase (phenylalanine hydroxylase, EC 1.14.16.1).", "entity1": "EC 1.14.16.1", "entity2": "Catecholamines", "span1": [139, 151], "span2": [0, 14]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3426": {"label": 1, "data": {"text": "The G719S/T790M double mutant has enhanced activity and retains high gefitinib-binding affinity.", "entity1": "T790M", "entity2": "gefitinib", "span1": [10, 15], "span2": [69, 78]}, "weak_labels": [-1, -1, 0, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6474": {"label": 3, "data": {"text": "Nordihydroguaiaretic acid (NDGA) has been shown to inhibit both 5-lipoxygenase and ornithine decarboxylase and is active against several cancer cell lines and at least one mouse tumor model.", "entity1": "5-lipoxygenase", "entity2": "Nordihydroguaiaretic acid", "span1": [64, 78], "span2": [0, 25]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7079": {"label": 2, "data": {"text": "However, human physiological studies demonstrate a paradoxical role of menthol in modulation of warm sensation, and here, we show that menthol also activates heat-activated TRPV3.", "entity1": "TRPV3", "entity2": "menthol", "span1": [173, 178], "span2": [135, 142]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2690": {"label": 3, "data": {"text": "Molecular modeling of the kinase domain of mutant c-Kit (V654A) and AXL showed no binding to IM but efficient binding to MP470, a novel c-Kit/AXL kinase inhibitor.", "entity1": "AXL", "entity2": "MP470", "span1": [142, 145], "span2": [121, 126]}, "weak_labels": [-1, -1, 0, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4645": {"label": 2, "data": {"text": "Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent activator of AhR.", "entity1": "CYP1A1", "entity2": "TCDD", "span1": [50, 56], "span2": [169, 173]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3092": {"label": 1, "data": {"text": "N-(Diphenylmethyl)-2-phenyl-4-quinazolinamine (SoRI-9804), N-(2,2-diphenylethyl)-2-phenyl-4-quinazolinamine (SoRI-20040), and N-(3,3-diphenylpropyl)-2-phenyl-4-quinazolinamine (SoRI-20041) partially inhibited [(125)I]3beta-(4'-iodophenyl)tropan-2beta-carboxylic acid methyl ester (RTI-55) binding, slowed the dissociation rate of [(125)I]RTI-55 from the DAT, and partially inhibited [(3)H]dopamine uptake.", "entity1": "DAT", "entity2": "SoRI-9804", "span1": [354, 357], "span2": [47, 56]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13779": {"label": 3, "data": {"text": "The following TK blockers for treatment of various human tumors are in clinical development: Lapatinib (Lapatinib ditosylate, Tykerb, GW-572016), Canertinib (CI-1033), Zactima (ZD6474), Vatalanib (PTK787/ZK 222584), Sorafenib (Bay 43-9006, Nexavar), and Leflunomide (SU101, Arava).", "entity1": "TK", "entity2": "GW-572016", "span1": [14, 16], "span2": [134, 143]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3658": {"label": 9, "data": {"text": "However, even in the presence of significant AChE inhibition, exposure to non-teratogenic paraoxon concentrations (\u2264250 nM) did not adversely impact secondary motoneuron development at 96 hpf.", "entity1": "AChE", "entity2": "paraoxon", "span1": [45, 49], "span2": [90, 98]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7283": {"label": 3, "data": {"text": "This reduction in TGF-beta2 is biologically relevant since PFD treatment reduces the growth inhibition of TGF-beta-sensitive CCL-64 cells mediated by conditioned media of glioma cells.", "entity1": "TGF-beta2", "entity2": "PFD", "span1": [18, 27], "span2": [59, 62]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9481": {"label": 1, "data": {"text": "The human ether-a-go-go-related gene (HERG), which encodes the rapidly activating delayed rectifier K+ current and is important in cardiac repolarization, may serve as a target for the action of cisapride.", "entity1": "human ether-a-go-go-related gene", "entity2": "cisapride", "span1": [4, 36], "span2": [195, 204]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9550": {"label": 1, "data": {"text": "In addition, the betaAR-mediated inhibition of IFN-gamma, GM-CSF, and IL-3 mRNA accumulation and GM-CSF protein secretion were related to the accumulation of intracellular cyclic adenosine monophosphate (cAMP) levels.", "entity1": "GM-CSF", "entity2": "cAMP", "span1": [58, 64], "span2": [204, 208]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5957": {"label": 9, "data": {"text": "Loperamide modifies but does not block the corticotropin-releasing hormone-induced ACTH response in patients with Addison's disease.", "entity1": "corticotropin-releasing hormone", "entity2": "Loperamide", "span1": [43, 74], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"144": {"label": 1, "data": {"text": "Although these findings might be explained by the involvement of different intracellular ACTH-secreting mechanisms, an influence of loperamide on some suprapituitary factors modulating the ACTH response is suggested.", "entity1": "ACTH", "entity2": "loperamide", "span1": [189, 193], "span2": [132, 142]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1908": {"label": 8, "data": {"text": "PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to 5-fluorouracil (5-FU) by thymidine phosphorylase (TP) inside target tissues.", "entity1": "thymidine phosphorylase", "entity2": "5-FU", "span1": [96, 119], "span2": [87, 91]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1]},
	"3904": {"label": 3, "data": {"text": "This stimulation was attenuated by the Pak inhibitor 2,2'-dihydroxy-1,1'-dinaphthyldisulfide (IPA3) or dominant-negative Pak1.", "entity1": "Pak", "entity2": "2,2'-dihydroxy-1,1'-dinaphthyldisulfide", "span1": [39, 42], "span2": [53, 92]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11564": {"label": 3, "data": {"text": "In HEK293 cells stably transfected with FLT3-WT or FLT3-ITD, sorafenib blocked basal and ligand dependent FLT3-mediated tyrosine autophosphorylation as well as extracellular signal-regulated kinase1/2 and Stat5 phosphorylation.", "entity1": "Stat5", "entity2": "sorafenib", "span1": [205, 210], "span2": [61, 70]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9716": {"label": 3, "data": {"text": "Preferential cerebrospinal fluid acetylcholinesterase inhibition by rivastigmine in humans.", "entity1": "acetylcholinesterase", "entity2": "rivastigmine", "span1": [33, 53], "span2": [68, 80]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12464": {"label": 1, "data": {"text": "The responses to 5-FU, with respect to both toxicity and efficacy, vary among racial groups, potentially because of variability in the activity levels of the enzyme dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene).", "entity1": "DPD", "entity2": "5-FU", "span1": [198, 201], "span2": [17, 21]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9826": {"label": 3, "data": {"text": "Moreover, geldanamycin decreases the amount and phosphorylation of Lck and Raf-1 kinases and prevents activation of the extracellular signal regulated kinase (ERK)-2 kinase.", "entity1": "Raf-1", "entity2": "geldanamycin", "span1": [75, 80], "span2": [10, 22]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3540": {"label": 1, "data": {"text": "Pretreatment with pranlukast (1.5 ng/mouse, intracerebroventricularly), a CysLT(1)R antagonist, blocked LTD4-induced amyloidogenesis, memory deficits.", "entity1": "CysLT(1)R", "entity2": "LTD4", "span1": [74, 83], "span2": [104, 108]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9896": {"label": 9, "data": {"text": "However, in virgin mice, bezafibrate and WY-14,643 do not significantly affect UCP-3 mRNA expression, whereas troglitazone is at least as effective as it is in lactating dams.", "entity1": "UCP-3", "entity2": "bezafibrate", "span1": [79, 84], "span2": [25, 36]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"12994": {"label": 1, "data": {"text": "The phenylmorpholines, of which amorolfine is the sole representative in human therapy, affect two targets in the ergosterol pathway: Erg24p (delta 14 reductase) and Erg2p (delta 8-delta 7 isomerase).", "entity1": "Erg2p", "entity2": "phenylmorpholines", "span1": [166, 171], "span2": [4, 21]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6730": {"label": 3, "data": {"text": "Compounds of several other structural families, including the quinoxaline AG1296, the bis(1H-2-indolyl)-1-methanone D-65476, the indolinones SU5416 and SU11248, the indolocarbazoles PKC412 and CEP-701, and the piperazonyl quinazoline CT53518, are potent inhibitors of Flt3 kinase.", "entity1": "Flt3", "entity2": "SU11248", "span1": [268, 272], "span2": [152, 159]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"695": {"label": 1, "data": {"text": "To illuminate the controversy on alpha 1A- or alpha 1L-adrenoceptor involvement in noradrenaline-mediated contractions of rat small mesenteric artery (SMA), we have studied the effects of subtype-selective alpha 1-adrenoceptor agonists and antagonists under different experimental conditions.", "entity1": "alpha 1A", "entity2": "noradrenaline", "span1": [33, 41], "span2": [83, 96]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14480": {"label": 8, "data": {"text": "The catalytic competence of cytochrome P450 in the synthesis of serotonin from 5-methoxytryptamine in the brain: an in vitro study.", "entity1": "cytochrome P450", "entity2": "serotonin", "span1": [28, 43], "span2": [64, 73]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13162": {"label": 5, "data": {"text": "5-HT3 receptor antagonism with alosetron reduced responses to 5-HT in controls but not during inflammation.", "entity1": "5-HT3 receptor", "entity2": "alosetron", "span1": [0, 14], "span2": [31, 40]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"4681": {"label": 1, "data": {"text": "For this purpose, C57BL6 mice were injected intraperitoneally with V(5+) (5\u00a0mg/kg) in the absence and presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (15\u00a0\u03bcg/kg) for 6 and 24\u00a0h. Furthermore, isolated hepatocytes from C57BL6 mice were treated with V(5+) (5, 10, and 20\u00a0\u03bcM) in the absence and presence of TCDD (1 nM) for 3, 6, 12, and 24\u00a0h. In vivo, V(5+) alone did not significantly alter Cyp1a1, Cyp1a2, or Cyp1b1 mRNA, protein, or catalytic activity levels.", "entity1": "Cyp1a1", "entity2": "V(5+)", "span1": [394, 400], "span2": [354, 359]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"8411": {"label": 3, "data": {"text": "Ponatinib (AP24534) is a multikinase inhibitor with in vitro and clinical activity in tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia, irrespective of BCR-ABL KD mutation.", "entity1": "multikinase", "entity2": "Ponatinib", "span1": [25, 36], "span2": [0, 9]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10091": {"label": 8, "data": {"text": "Three replicate studies in the oral surgery model of acute pain used submucosal microdialysis sample collection for the measurement of prostaglandin E2 (PGE2; a product of both COX-1 and COX-2) and thromboxane B2 (as a biomarker for COX-1 activity) with parallel assessments of pain.", "entity1": "COX-2", "entity2": "prostaglandin E2", "span1": [187, 192], "span2": [135, 151]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"13956": {"label": 3, "data": {"text": "Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity.", "entity1": "monoamine oxidase-B", "entity2": "Rasagiline", "span1": [38, 57], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13828": {"label": 8, "data": {"text": "Atomoxetine appeared better tolerated among extensive CYP2D6 metabolizers than among poor metabolizers.", "entity1": "CYP2D6", "entity2": "Atomoxetine", "span1": [54, 60], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11702": {"label": 1, "data": {"text": "We report that wogonoside triggered the formation of microtubule-associated protein-light chain 3 (MAP-LC3) positive autophagosomes and the accumulation of acidic vesicular and autolysosomes in MDA-MB-231 cells.", "entity1": "MAP-LC3", "entity2": "wogonoside", "span1": [99, 106], "span2": [15, 25]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10363": {"label": 2, "data": {"text": "In addition the production of BrBK1-8 was enhanced in the presence of these inhibitors with a greater accumulation being observed with omapatrilat.", "entity1": "BrBK1-8", "entity2": "omapatrilat", "span1": [30, 37], "span2": [135, 146]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"11440": {"label": 1, "data": {"text": "We also studied the effects of thalidomide on COX-1, COX-2 or bcl-2 expression, TNFalpha, VEGF, GSH and cytochrome c in these cells.", "entity1": "bcl-2", "entity2": "thalidomide", "span1": [62, 67], "span2": [31, 42]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3195": {"label": 3, "data": {"text": "Phenols like the ones investigated here possess a CA inhibition mechanism distinct of that of the sulfonamides/sulfamates used clinically or the coumarins.", "entity1": "CA", "entity2": "coumarins", "span1": [50, 52], "span2": [145, 154]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13712": {"label": 3, "data": {"text": "CONCLUSIONS AND IMPLICATIONS: Halogenated propofol analogues constitute a novel class of sodium channel-blocking drugs possessing almost 100-fold higher potency compared with the local anaesthetic and anti-arrhythmic drug lidocaine.", "entity1": "sodium channel", "entity2": "Halogenated propofol", "span1": [89, 103], "span2": [30, 50]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5277": {"label": 3, "data": {"text": "Allicin treatment showed reduced production of pro-inflammatory cytokines and NO and increased HO-1 activity.", "entity1": "cytokines", "entity2": "Allicin", "span1": [64, 73], "span2": [0, 7]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"12714": {"label": 3, "data": {"text": "However, when coapplied with 10 micro m GABA, ivermectin potentiated the GABA-evoked current of the GAB-1/HG1A receptor, but attenuated the GABA response of the GAB-1/HG1E receptor.", "entity1": "GAB-1", "entity2": "ivermectin", "span1": [161, 166], "span2": [46, 56]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5218": {"label": 2, "data": {"text": "In addition, vinblastine induces the DNA-binding activities of the transcription factor NF-\u03baB, HSF1, AP-1, and ATF-2, together with the expression of HSP70 and Bax proteins.", "entity1": "ATF-2", "entity2": "vinblastine", "span1": [111, 116], "span2": [13, 24]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1112": {"label": 2, "data": {"text": "CONCLUSIONS: Our results show that indomethacin, a known cyclooxygenase (COX) inhibitor, is also an activator of CA.", "entity1": "CA", "entity2": "indomethacin", "span1": [113, 115], "span2": [35, 47]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"473": {"label": 1, "data": {"text": "However, at guinea-pig and mouse splenic alpha 1B-adrenoceptors, the affinity values of risperidone were 10-fold lower than those of prazosin.", "entity1": "guinea-pig and mouse splenic alpha 1B-adrenoceptors", "entity2": "risperidone", "span1": [12, 63], "span2": [88, 99]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5692": {"label": 3, "data": {"text": "In a neuronal cell line, we found that selective CB(2) receptor agonists upregulate \u03b2-Arrestin 2, an effect that was prevented by selective CB(2) receptor antagonist JTE-907 and CB(2) shRNA lentiviral particles.", "entity1": "\u03b2-Arrestin 2", "entity2": "JTE-907", "span1": [84, 96], "span2": [166, 173]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5778": {"label": 1, "data": {"text": "Inhibition of binding of both plasminogen and plasmin to gp330 by benzamidine was similar, although EACA inhibited the binding of plasmin to gp330 slightly more than the binding of plasminogen to gp330.", "entity1": "gp330", "entity2": "benzamidine", "span1": [57, 62], "span2": [66, 77]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15974": {"label": 1, "data": {"text": "Mechanistic Aspects of hSOD1 Maturation from the Solution Structure of Cu(I) -Loaded hCCS Domain 1 and Analysis of Disulfide-Free hSOD1 Mutants.", "entity1": "hCCS Domain 1", "entity2": "Cu(I)", "span1": [85, 98], "span2": [71, 76]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8035": {"label": 2, "data": {"text": "Dietary carbohydrates increase SCD-1 gene expression in liver by sterol response element binding protein (SREBP)-1c-dependent and SREBP-1c -independent pathways.", "entity1": "SCD-1", "entity2": "carbohydrates", "span1": [31, 36], "span2": [8, 21]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13813": {"label": 3, "data": {"text": "Others kinase inhibitors used recently in cancer therapy include Dasatinib (BMS-354825) specific for ABL non-receptor cytoplasmic kinase, Gefitinib (Iressa), Erlotinib (OSI-774, Tarceva) and Sunitinib (SU 11248, Sutent) specific for VEGF receptor kinase, AMN107 (Nilotinib) and INNO-406 (NS-187) specific for c-KIT kinase.", "entity1": "kinase", "entity2": "Erlotinib", "span1": [247, 253], "span2": [158, 167]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4346": {"label": 3, "data": {"text": "Subsequently, pinosylvin suppressed the nuclear translocation of \u03b2-catenin, one of downstream molecules of PI3K/Akt/GSK-3\u03b2 signaling, and these events led to the sequential downregulation of \u03b2-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc.", "entity1": "PI3K", "entity2": "pinosylvin", "span1": [107, 111], "span2": [14, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12603": {"label": 0, "data": {"text": "The predicted structure of PHBP showed three epidermal growth factor (EGF) domains, a kringle domain and a serine protease domain, from its N-terminus, although HGFA has a fibronectin type II domain, an EGF domain, a fibronectin type I domain, an EGF domain, a kringle domain, and a serine protease domain, from its N-terminus.", "entity1": "EGF domain", "entity2": "N", "span1": [247, 257], "span2": [316, 317]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7960": {"label": 5, "data": {"text": "UCCB01-125, a dimeric inhibitor of PSD-95, reduces inflammatory pain without disrupting cognitive or motor performance: comparison with the NMDA receptor antagonist MK-801.", "entity1": "NMDA receptor", "entity2": "MK-801", "span1": [140, 153], "span2": [165, 171]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"612": {"label": 1, "data": {"text": "Therefore, the objective of the present study was to investigate the effects of PLA2 inhibitors p-bromophenacyl bromide (BPB) and arachidonyl trifluoromethyl ketone (AACOCF3) on interleukin-2 (IL-2) expression in murine primary splenocytes.", "entity1": "IL-2", "entity2": "arachidonyl trifluoromethyl ketone", "span1": [193, 197], "span2": [130, 164]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15737": {"label": 8, "data": {"text": "These results indicate that parabens are selective agonists for ER\u03b2 over ER\u03b1; their interactions with ER\u03b1/\u03b2 are dependent on the size and bulkiness of the alkyl groups; and they are metabolized by carboxylesterases, leading to attenuation of their estrogenic activity.", "entity1": "carboxylesterases", "entity2": "parabens", "span1": [197, 214], "span2": [28, 36]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14592": {"label": 3, "data": {"text": "In addition, 17-AAG treatment reduced cell viability, CDK2, CDK4, cyclin E, cyclin D1, and phosphorylated Rb levels in AhR-expressing lung AD cells.", "entity1": "CDK4", "entity2": "17-AAG", "span1": [60, 64], "span2": [13, 19]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2905": {"label": 3, "data": {"text": "Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man.", "entity1": "cyclooxygenase-2", "entity2": "Acetaminophen", "span1": [43, 59], "span2": [0, 13]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8295": {"label": 2, "data": {"text": "LY294002, a specific PI3K/AKT inhibitor, selectively activated the p38 MAPK kinase pathway and enhanced c-Jun phosphorylation, but did not activate JNK.", "entity1": "c-Jun", "entity2": "LY294002", "span1": [104, 109], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"8767": {"label": 5, "data": {"text": "SB225002 (SB) is an IL-8 receptor B (IL-8RB) antagonist that has previously been shown to inhibit IL-8-based cancer cell invasion, and to possess in vivo anti-inflammatory and anti-nociceptive effects.", "entity1": "IL-8RB", "entity2": "SB225002", "span1": [37, 43], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4924": {"label": 2, "data": {"text": "Activation of ALDH2 with ethanol attenuates diabetes induced myocardial injury in rats.", "entity1": "ALDH2", "entity2": "ethanol", "span1": [14, 19], "span2": [25, 32]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7088": {"label": 3, "data": {"text": "These currents were produced by glutamate-aspartate transporters (GLAST) (excitatory amino acid transporter 1) because they were weakly inhibited by dihydrokainate, an antagonist of glutamate transporter-1 (excitatory amino acid transporter 2) and were absent from IPCs in GLAST-/- cochleas.", "entity1": "GLAST", "entity2": "dihydrokainate", "span1": [66, 71], "span2": [149, 163]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, 8, -1, 8, -1, -1]},
	"6752": {"label": 3, "data": {"text": "Although highly homologous to other class III RTKs, Flt3 is resistant to the phenylaminopyrimidine STI571 (Gleevec, Imatinib), a potent inhibitor of other RTKs in the family, such as the PDGFbeta-receptor or c-Kit.", "entity1": "PDGFbeta-receptor", "entity2": "Imatinib", "span1": [187, 204], "span2": [116, 124]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13341": {"label": 2, "data": {"text": "In addition, activation of protein kinase C and increases in intracellular cAMP also enhance cholinergic activity in T cells, and lymphocyte function associated antigen-1 (LFA-1; CD11a/CD18) is an important mediator of leukocyte migration and T cell activation.", "entity1": "CD11a", "entity2": "cAMP", "span1": [179, 184], "span2": [75, 79]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7233": {"label": 3, "data": {"text": "GnRH-induced Pyk2 activation opposed the association of Hic-5 with androgen receptor as overexpression of a dominant negative Pyk2 enhanced the GnRH-induced nuclear translocation of a green fluorescent protein-tagged human androgen receptor.", "entity1": "Hic-5", "entity2": "GnRH", "span1": [56, 61], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6801": {"label": 1, "data": {"text": "Levetiracetam binds selectively and with high affinity to a synaptic vesicle protein known as SV2A, thought to be involved with synaptic vesicle exocytosis and presynaptic neurotransmitter release.", "entity1": "SV2A", "entity2": "Levetiracetam", "span1": [94, 98], "span2": [0, 13]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13042": {"label": 8, "data": {"text": "Here we demonstrate that PPARgamma, turns on retinoic acid synthesis by inducing the expression of retinol and retinal metabolizing enzymes such as retinol dehydrogenase 10 and retinaldehyde dehydrogenase type 2 (RALDH2).", "entity1": "retinol dehydrogenase 10", "entity2": "retinoic acid", "span1": [148, 172], "span2": [45, 58]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11199": {"label": 1, "data": {"text": "In the current studies, we show that two different classes (ATP-sensitive and -insensitive) of TOP2 poisons can be identified based on their differential sensitivity to the ATP-bound conformation of TOP2.", "entity1": "TOP2", "entity2": "ATP", "span1": [199, 203], "span2": [173, 176]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3260": {"label": 3, "data": {"text": "The contractions to 5-HT were inhibited by ketanserin and alosetron indicating involvement of 5-HT(2A) and 5-HT(3) receptors, respectively.", "entity1": "5-HT(2A)", "entity2": "ketanserin", "span1": [94, 102], "span2": [43, 53]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5929": {"label": 3, "data": {"text": "It is proposed that two molecules of estramustine phosphate interact with each of the three tubulin-binding sites of MAP2 and inhibit the MAP2:tubulin interaction by neutralising two highly conserved basic residues.", "entity1": "MAP2", "entity2": "estramustine phosphate", "span1": [138, 142], "span2": [37, 59]}, "weak_labels": [-1, -1, -1, 1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12455": {"label": 2, "data": {"text": "This report concerns the marked up-regulation in differentiated CaCo-2 colonic epithelial cells of two key inflammatory interleukins, IL-6 and IL-8, caused by a mixture of oxysterols representative of a high cholesterol diet.", "entity1": "interleukins", "entity2": "oxysterols", "span1": [120, 132], "span2": [172, 182]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15283": {"label": 1, "data": {"text": "Mice given daily injections of high dose JZL184 (\u226516 mg/kg) for six days displayed decreased CB(1) receptor density and function in brain, as assessed in [(3)H]SR141716A binding and CP55,940-stimulated [(35)S]GTP\u03b3S binding assays, respectively.", "entity1": "CB(1)", "entity2": "CP55,940", "span1": [93, 98], "span2": [182, 190]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13746": {"label": 1, "data": {"text": "Inhibition of (+)-[(3)H]isradipine binding to Ca(v)1.2DHP(-/-) (predominantly Ca(v)1.3) and wild-type (predominantly Ca(v)1.2) brain membranes by unlabeled DHPs revealed a 3- to 4-fold selectivity of nitrendipine and nifedipine for the Ca(v)1.2 binding pocket, a finding further confirmed with heterologously expressed channels.", "entity1": "Ca(v)1.2", "entity2": "nitrendipine", "span1": [236, 244], "span2": [200, 212]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11336": {"label": 3, "data": {"text": "In the present study, we measured the enzyme activity of thymidine kinase (TK), thymidine phosphorylase (TP) and thymidilate synthase (TS) in human cancer xenografts to investigate the contribution of these enzymes to the sensitivity of TAS-102.", "entity1": "TS", "entity2": "TAS-102", "span1": [135, 137], "span2": [237, 244]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2497": {"label": 3, "data": {"text": "Licofelone, a dual anti-inflammatory drug that inhibits 5-lipoxygenase (LOX) and cyclooxygenase (COX) enzymes, may have a better cardiovascular profile that cycloxygenase-2 inhibitors due to cycloxygenase-1 blockade-mediated antithrombotic effect and a better gastrointestinal tolerability.", "entity1": "cyclooxygenase", "entity2": "Licofelone", "span1": [81, 95], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11325": {"label": 1, "data": {"text": "However, NMDA receptors appear to be a key target of memantine at therapeutic concentrations.", "entity1": "NMDA receptors", "entity2": "memantine", "span1": [9, 23], "span2": [53, 62]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10951": {"label": 8, "data": {"text": "These results provide biochemical evidence of a H(+)-coupled and saturable transport system, presumed to be a low-affinity monocarboxylate transporter MCT4 or other unknown H(+)-coupled monocarboxylate transport system, for nicotinate in rat cerebrocortical astrocytes.", "entity1": "low-affinity monocarboxylate transporter", "entity2": "nicotinate", "span1": [110, 150], "span2": [224, 234]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"713": {"label": 3, "data": {"text": "Isometric contraction induced by a submaximal concentration of Ang II (10(-7) mol/L) was reduced in a dose-dependent way by torasemide (IC(50)=0.5+/-0.04 micromol/L).", "entity1": "Ang II", "entity2": "torasemide", "span1": [63, 69], "span2": [124, 134]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8459": {"label": 3, "data": {"text": "Hinokitiol inhibited the phosphorylation of phospholipase C (PLC)\u03b32, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and Akt in collagen-activated human platelets, and significantly reduced intracellular calcium mobilization and hydroxyl radical (OH) formation.", "entity1": "mitogen-activated protein kinases", "entity2": "Hinokitiol", "span1": [93, 126], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5190": {"label": 3, "data": {"text": "Treatment of A549 and H1299 cells with dioscin caused a dose-dependent increase in ERK1/2 and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR.", "entity1": "PI3K", "entity2": "dioscin", "span1": [140, 144], "span2": [39, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8533": {"label": 2, "data": {"text": "Besides, CDM not only synergized TNF-\u03b1 production combined with IFN-\u03b3, but also prolonged its expression in time.", "entity1": "TNF-\u03b1", "entity2": "CDM", "span1": [33, 38], "span2": [9, 12]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 9]},
	"2403": {"label": 1, "data": {"text": "To determine whether arginases modulate the endothelial NO synthesis, we investigated the effects of the competitive arginase inhibitor N(omega)-hydroxy-nor-L-arginine (Nor-NOHA) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs).", "entity1": "NOS", "entity2": "N(omega)-hydroxy-nor-L-arginine", "span1": [198, 201], "span2": [136, 167]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, 6, -1, -1, -1, 8, -1, -1, -1, -1]},
	"4812": {"label": 3, "data": {"text": "Several members of a new family of non-sugar-type \u03b1-glycosidase inhibitors, bearing a 5-(p-toluenesulfonylamino)phthalimide moiety and various substituent at the N2 position, were synthesized and their activities were investigated.", "entity1": "\u03b1-glycosidase", "entity2": "5-(p-toluenesulfonylamino)phthalimide", "span1": [50, 63], "span2": [86, 123]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14896": {"label": 3, "data": {"text": "In mice, this reduction in FMO3 expression is due primarily to downregulation by androgens.", "entity1": "FMO3", "entity2": "androgens", "span1": [27, 31], "span2": [81, 90]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3307": {"label": 1, "data": {"text": "Steady-state fluorescence was utilized to assess Ca(2+) affinity in isolated cardiac (c)TnCs containing F27W and did not necessarily mirror the fiber Ca(2+) sensitivity.", "entity1": "F27W", "entity2": "Ca(2+)", "span1": [104, 108], "span2": [49, 55]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"13385": {"label": 1, "data": {"text": "To provide insights into how sirtuin function is altered by inhibitors, we determined two crystal structures of SIRT5, one in complex with ADP-ribose, the other bound to suramin.", "entity1": "SIRT5", "entity2": "suramin", "span1": [112, 117], "span2": [170, 177]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11438": {"label": 1, "data": {"text": "We also studied the effects of thalidomide on COX-1, COX-2 or bcl-2 expression, TNFalpha, VEGF, GSH and cytochrome c in these cells.", "entity1": "COX-1", "entity2": "thalidomide", "span1": [46, 51], "span2": [31, 42]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1473": {"label": 8, "data": {"text": "Interestingly, the allele of PRO1 was shown to enhance the activities of gamma-glutamyl kinase and gamma-glutamyl phosphate reductase, both of which catalyze the first two steps of L-proline synthesis from L-glutamate and which together may form a complex in vivo.", "entity1": "gamma-glutamyl kinase", "entity2": "L-glutamate", "span1": [73, 94], "span2": [206, 217]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"4066": {"label": 3, "data": {"text": "Among the isolated compounds, trans-dihydromorin (8), oxyresveratrol (9), and steppogenin (12) were found to exhibit significant tyrosinase inhibition activities.", "entity1": "tyrosinase", "entity2": "steppogenin", "span1": [129, 139], "span2": [78, 89]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3321": {"label": 1, "data": {"text": "VP-16 induced the release of IL-8, and addition of MXF reduced enhanced release and the spontaneous release of VEGF from the cells.", "entity1": "VEGF", "entity2": "MXF", "span1": [111, 115], "span2": [51, 54]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4711": {"label": 3, "data": {"text": "Thus, the TCDD-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway.", "entity1": "Rspo2", "entity2": "TCDD", "span1": [105, 110], "span2": [10, 14]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, 2, -1, -1, -1, 3, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3805": {"label": 3, "data": {"text": "The two basic mainstays of gastrointestinal stromal tumours (GIST) treatment are surgery and imatinib, a selective tyrosine kinase inhibitor that allows achieving a stable or responding disease in about 80% of patients with unresectable/metastatic GIST.", "entity1": "tyrosine kinase", "entity2": "imatinib", "span1": [115, 130], "span2": [93, 101]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9536": {"label": 8, "data": {"text": "System y+ cationic amino acid transport is mediated by proteins encoded by a family of genes, Cat1, Cat2, and Cat3.", "entity1": "Cat2", "entity2": "amino acid", "span1": [100, 104], "span2": [19, 29]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"6379": {"label": 3, "data": {"text": "Thirty-week administration of UFT with or without leucovorin markedly suppressed both colorectal carcinogenesis and tumor growth, resulted in the increase of thymidylate synthase inhibition and the decrease of thymidine kinase activity in the tumor cells.", "entity1": "thymidylate synthase", "entity2": "leucovorin", "span1": [158, 178], "span2": [50, 60]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9039": {"label": 8, "data": {"text": "Interference with lipoxygenase enzymes, rather than a steroid-like inhibition of arachidonic acid release from intracellular phospholipids, seems to be the mode of action.", "entity1": "lipoxygenase", "entity2": "arachidonic acid", "span1": [18, 30], "span2": [81, 97]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9930": {"label": 9, "data": {"text": "Activation of extracellular signal-related kinase (ERK) 1 and 2, c-Jun-N-terminal kinase (JNK) 1, and p38 was unaffected by sulfasalazine.", "entity1": "c-Jun-N-terminal kinase (JNK) 1", "entity2": "sulfasalazine", "span1": [65, 96], "span2": [124, 137]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1705": {"label": 8, "data": {"text": "These findings demonstrate that PEPT2 is the primary transporter responsible for cefadroxil uptake in the choroid plexus.", "entity1": "PEPT2", "entity2": "cefadroxil", "span1": [32, 37], "span2": [81, 91]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"5087": {"label": 1, "data": {"text": "PKD1 and PI4KIII\u03b2 localize to the TGN, and aldosterone induced an interaction between PKD1 and PI4KIII\u03b2 following aldosterone treatment.", "entity1": "PKD1", "entity2": "aldosterone", "span1": [86, 90], "span2": [43, 54]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10906": {"label": 8, "data": {"text": "Pyridoxal kinase (PDXK) catalyzes the phosphorylation of pyridoxal, pyridoxamine, and pyridoxine in the presence of ATP and Zn2+.", "entity1": "PDXK", "entity2": "pyridoxal", "span1": [18, 22], "span2": [57, 66]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"8330": {"label": 3, "data": {"text": "In particular, we showed that Paeoniflorin significantly reduced the formation of intracellular reactive oxygen species (ROS), the level of malondialdehyde (MDA) and lactate dehydrogenase (LDH) leakage, and enhanced production of the endogenous antioxidants, glutathione (GSH) and superoxide dismutase (SOD) in EA.hy926 cells.", "entity1": "LDH", "entity2": "Paeoniflorin", "span1": [189, 192], "span2": [30, 42]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"1498": {"label": 3, "data": {"text": "Sulindac and selective cyclooxygenase (COX)-2 inhibitors cause regression of colonic polyps in familial polyposis patients.", "entity1": "cyclooxygenase (COX)-2", "entity2": "Sulindac", "span1": [23, 45], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15300": {"label": 3, "data": {"text": "Fragment-based drug design and identification of HJC0123, a novel orally bioavailable STAT3 inhibitor for cancer therapy.", "entity1": "STAT3", "entity2": "HJC0123", "span1": [86, 91], "span2": [49, 56]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8489": {"label": 3, "data": {"text": "Furthermore, no impact on cytokine release (i.e., on IL-10, IL-6, IL-12/23p40 and TNF\u03b1 levels) was seen in LPS-stimulated human PBMCs, except with JWH-210 and JWH-122 which caused a decrease of TNF\u03b1 and IL-12/23p40.", "entity1": "IL-12", "entity2": "JWH-122", "span1": [203, 208], "span2": [159, 166]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15090": {"label": 3, "data": {"text": "Avibactam (formerly NXL104, AVE1330A) is a synthetic non-\u03b2-lactam, \u03b2-lactamase inhibitor that inhibits the activities of Ambler class A and C \u03b2-lactamases and some Ambler class D enzymes.", "entity1": "Ambler class D", "entity2": "NXL104", "span1": [164, 178], "span2": [20, 26]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14331": {"label": 3, "data": {"text": "Results showed that DMF increased nuclear levels of Nrf2, and both DMF and adenovirus-mediated overexpression of Nrf2 (Ad-Nrf2) decreased PAI-1, alpha-smooth muscle actin (alpha-SMA), fibronectin and type 1 collagen expression in TGF-beta-treated rat mesangial cells (RMCs) and renal fibroblast cells (NRK-49F).", "entity1": "fibronectin", "entity2": "DMF", "span1": [184, 195], "span2": [67, 70]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15100": {"label": 3, "data": {"text": "Ceftazidime-avibactam: a novel cephalosporin/\u03b2-lactamase inhibitor combination.", "entity1": "\u03b2-lactamase", "entity2": "Ceftazidime", "span1": [45, 56], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4326": {"label": 3, "data": {"text": "Pinosylvin inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53.", "entity1": "CDK2", "entity2": "Pinosylvin", "span1": [204, 208], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 2, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"635": {"label": 3, "data": {"text": "Therefore, the objective of the present study was to investigate the effects of PLA2 inhibitors p-bromophenacyl bromide (BPB) and arachidonyl trifluoromethyl ketone (AACOCF3) on interleukin-2 (IL-2) expression in murine primary splenocytes.", "entity1": "PLA2", "entity2": "BPB", "span1": [80, 84], "span2": [121, 124]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1633": {"label": 1, "data": {"text": "AIM: To study the changes in the expression and phosphorylation of cAMP response element binding protein (CREB) in the rat nucleus accumbens after chronic ethanol intake and its withdrawal.", "entity1": "cAMP response element binding protein", "entity2": "ethanol", "span1": [67, 104], "span2": [155, 162]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7073": {"label": 3, "data": {"text": "The cholesterol-lowering drug simvastatin inhibits LFA-1 signaling by binding to an allosteric site on CD11a (LFA-1 alpha chain), which leads to immunomodulation.", "entity1": "LFA-1", "entity2": "simvastatin", "span1": [51, 56], "span2": [30, 41]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, 6, 6, -1, -1, -1, -1, -1, -1, -1]},
	"9557": {"label": 1, "data": {"text": "Concanavalin A (Con A)-induced IFN-gamma, GM-CSF, and IL-3 mRNAs are dose-dependently inhibited by the nonselective betaAR agonist isoproterenol and by the selective beta2AR agonist fenoterol.", "entity1": "Concanavalin A", "entity2": "fenoterol", "span1": [0, 14], "span2": [182, 191]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"12256": {"label": 2, "data": {"text": "Estrogen protects against mitochondrial dysfunction caused by excitotoxicity by maintaining cellular redox status through higher constitutive expression of glutaredoxin in the CNS.", "entity1": "glutaredoxin", "entity2": "Estrogen", "span1": [156, 168], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"690": {"label": 1, "data": {"text": "Combined concentration-ratio analysis demonstrated that tamsulosin, which does not discriminate between alpha 1A- and alpha 1L-adrenoceptors, and RS-17053 competed for binding at the same site in the SMA.", "entity1": "alpha 1L-adrenoceptors", "entity2": "tamsulosin", "span1": [118, 140], "span2": [56, 66]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"4810": {"label": 3, "data": {"text": "PF-04859989 as a template for structure-based drug design: identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency.", "entity1": "KAT II", "entity2": "pyrazole", "span1": [113, 119], "span2": [81, 89]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8137": {"label": 3, "data": {"text": "Isoproterenol induced myocardial infarcted rats showed a significant increase in the levels of cardiac diagnostic markers, heart mitochondrial lipid peroxidation, calcium, and a significant decrease in the activities/levels of heart mitochondrial glutathione peroxidase, glutathione reductase, reduced glutathione, isocitrate, succinate, malate, \u03b1-ketoglutarate and NADH-dehydrogenases, cytochrome-C-oxidase and adenosine triphosphate.", "entity1": "glutathione peroxidase", "entity2": "Isoproterenol", "span1": [247, 269], "span2": [0, 13]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1788": {"label": 1, "data": {"text": "Tamsulosin, which has high affinity for alpha1aAR and alpha1dAR subtypes but not for alpha1bAR, shows efficacy similar to the nonsubtype selective agents terazosin and doxazosin.", "entity1": "alpha1bAR", "entity2": "doxazosin", "span1": [85, 94], "span2": [168, 177]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"8824": {"label": 3, "data": {"text": "Exhibiting unique properties over other MMPIs (e.g., hydroxamates), these newly reported compounds are capable of modulating activities of several MMPs in the low nanomolar range, including MMP-2 (~2 to 50 nM), MMP-13 (~2 to 50 nM), and MMP-14 (~4 to 60 nM).", "entity1": "MMP-2", "entity2": "hydroxamates", "span1": [190, 195], "span2": [53, 65]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2631": {"label": 3, "data": {"text": "The growth of the FLT3-independent RS4-11 cell line was only weakly inhibited by sorafenib.", "entity1": "FLT3", "entity2": "sorafenib", "span1": [18, 22], "span2": [81, 90]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6564": {"label": 3, "data": {"text": "Our study implies that highly conserved residuals Y751, D950 and F1004 in the PDE families are key residues for binding of both substrate and inhibitors, and nonconserved T844 may be responsible for the cilostazol selectivity of PDE3A.", "entity1": "PDE3A", "entity2": "cilostazol", "span1": [229, 234], "span2": [203, 213]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"15481": {"label": 3, "data": {"text": "Glutathione-S-transferase, a phase II enzyme, was inhibited by both arsenic and nicotine but no such inhibition was noted in arsenic-treated animals pre-exposed to nicotine.", "entity1": "Glutathione-S-transferase", "entity2": "nicotine", "span1": [0, 25], "span2": [80, 88]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"8227": {"label": 1, "data": {"text": "Together these findings suggest that ICA binds to the same site in EAG and ERG channels to elicit opposite functional effects.", "entity1": "EAG", "entity2": "ICA", "span1": [67, 70], "span2": [37, 40]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15773": {"label": 3, "data": {"text": "Both ICI treatments, induced a significant decrease (p<0.01) in uterine estrogen receptor alpha (ER\u03b1) content, had no effect on uterine progesterone receptor (PR) protein expression and caused marked nuclear localization of cyclin D1, in both luminal and glandular uterine epithelium, as compared to vehicle-treated animals.", "entity1": "estrogen receptor alpha", "entity2": "ICI", "span1": [72, 95], "span2": [5, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"506": {"label": 3, "data": {"text": "The results suggest that the 63-kDa (PDE 1B1) and 60-kDa (PDE 1A2) CaMPDE isozymes are inhibited by felodipine and nicardipine by partial competitive inhibition and that these two Ca2+ antagonists appear to counteract each other.", "entity1": "PDE 1B1", "entity2": "nicardipine", "span1": [37, 44], "span2": [115, 126]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3876": {"label": 2, "data": {"text": "However, combined treatment with cinobufagin and SB216367 resulted in a significant reduction in p65 and an increase in cleaved-PARP in U2OS cells.", "entity1": "PARP", "entity2": "cinobufagin", "span1": [128, 132], "span2": [33, 44]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7395": {"label": 3, "data": {"text": "Results of early clinical trials with both topically (cipamfylline, CP80,633) and systemically (CC-10004) active PDE4 inhibitors demonstrated efficacy in atopic dermatitis and in the case of CC-10004, also in psoriasis.", "entity1": "PDE4", "entity2": "cipamfylline", "span1": [113, 117], "span2": [54, 66]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7280": {"label": 3, "data": {"text": "Here, we report that the antifibrotic drug 5-methyl-1-phenyl-2-(1H)-pyridone (pirfenidone, PFD) elicits growth-inhibitory effects and reduces TGF-beta2 protein levels in human glioma cell lines.", "entity1": "TGF-beta2", "entity2": "5-methyl-1-phenyl-2-(1H)-pyridone", "span1": [142, 151], "span2": [43, 76]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12434": {"label": 2, "data": {"text": "Enhancement of GLUT4 expression by fisetin was further confirmed in differentiated 3T3-L1 adipocytes.", "entity1": "GLUT4", "entity2": "fisetin", "span1": [15, 20], "span2": [35, 42]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6774": {"label": 1, "data": {"text": "RESULTS: Aspirin, diclofenac, indomethacin, ketoprofen, meclofenamic acid, and piroxicam had little selectivity toward COX isozymes, whereas NS398, carprofen, tolfenamic acid, nimesulide, and etodolac had more than 5 times greater preference for inhibiting COX-2 than COX-1.", "entity1": "COX", "entity2": "ketoprofen", "span1": [119, 122], "span2": [44, 54]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1173": {"label": 3, "data": {"text": "Mitiglinide (KAD-1229), a new anti-diabetic drug, is thought to stimulate insulin secretion by closing the ATP-sensitive K+ (K(ATP)) channels in pancreatic beta-cells.", "entity1": "ATP-sensitive K+ (K(ATP)) channels", "entity2": "KAD-1229", "span1": [107, 141], "span2": [13, 21]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8840": {"label": 1, "data": {"text": "CONCLUSION: We provided documentation of neuroprotective effect of a natural flavone, calycopterin, against H2O2-induced oxidative stress in differentiated PC12 cells by modulating the level of CREB phosphorylation and Nrf2 pathway.", "entity1": "CREB", "entity2": "H2O2", "span1": [194, 198], "span2": [108, 112]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1421": {"label": 3, "data": {"text": "Stereospecific inhibition of monoamine uptake transporters by meta-hydroxyephedrine isomers.", "entity1": "monoamine uptake transporters", "entity2": "meta-hydroxyephedrine", "span1": [29, 58], "span2": [62, 83]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"1920": {"label": 8, "data": {"text": "The M564G mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, acetyl-CoA.", "entity1": "CrAT", "entity2": "acetyl-CoA", "span1": [18, 22], "span2": [210, 220]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"4808": {"label": 3, "data": {"text": "The structure-based design, synthesis, and biological evaluation of a new pyrazole series of irreversible KAT II inhibitors are described herein.", "entity1": "KAT II", "entity2": "pyrazole", "span1": [106, 112], "span2": [74, 82]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12787": {"label": 3, "data": {"text": "Valdecoxib showed similar activity in the human whole-blood COX assay (COX-2 IC(50) = 0.24 microM; COX-1 IC(50) = 21.9 microM).", "entity1": "human whole-blood COX", "entity2": "Valdecoxib", "span1": [42, 63], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13788": {"label": 3, "data": {"text": "The following TK blockers for treatment of various human tumors are in clinical development: Lapatinib (Lapatinib ditosylate, Tykerb, GW-572016), Canertinib (CI-1033), Zactima (ZD6474), Vatalanib (PTK787/ZK 222584), Sorafenib (Bay 43-9006, Nexavar), and Leflunomide (SU101, Arava).", "entity1": "TK", "entity2": "Bay 43-9006", "span1": [14, 16], "span2": [227, 238]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2670": {"label": 3, "data": {"text": "Administration of a concentration (100 microM) of dipyridamole that blocks PDE8 inhibited ecto-phosphodiesterase activity (by 44%).", "entity1": "phosphodiesterase", "entity2": "dipyridamole", "span1": [95, 112], "span2": [50, 62]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5643": {"label": 2, "data": {"text": "Arsenic trioxide-induced hERG K(+) channel deficiency can be rescued by matrine and oxymatrine through up-regulating transcription factor Sp1 expression.", "entity1": "transcription factor Sp1", "entity2": "oxymatrine", "span1": [117, 141], "span2": [84, 94]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2701": {"label": 2, "data": {"text": "Sitagliptin, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide.", "entity1": "incretin hormones", "entity2": "Sitagliptin", "span1": [130, 147], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"6753": {"label": 3, "data": {"text": "Although highly homologous to other class III RTKs, Flt3 is resistant to the phenylaminopyrimidine STI571 (Gleevec, Imatinib), a potent inhibitor of other RTKs in the family, such as the PDGFbeta-receptor or c-Kit.", "entity1": "c-Kit", "entity2": "Imatinib", "span1": [208, 213], "span2": [116, 124]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11464": {"label": 1, "data": {"text": "Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells.", "entity1": "EP1", "entity2": "prostaglandins", "span1": [15, 18], "span2": [77, 91]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2065": {"label": 9, "data": {"text": "As a result, we demonstrated that the apoE3 significantly protects these cells from GMC-induced reduction in AMG uptake, but neither lactoferrin nor albumin does.", "entity1": "albumin", "entity2": "GMC", "span1": [149, 156], "span2": [84, 87]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11559": {"label": 3, "data": {"text": "Development and validation of a non-radioactive DNA polymerase assay for studying cytomegalovirus resistance to foscarnet.", "entity1": "DNA polymerase", "entity2": "foscarnet", "span1": [48, 62], "span2": [112, 121]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6302": {"label": 5, "data": {"text": "These responses were effectively blocked by the 5-HT1B receptor antagonist, isamoltane, the 5-HT1B/5-HT2 receptor antagonist, methiothepin, and the eNOS selective antagonists (0.01-10 microM): L-Nomega -monomethyl-L-arginine (L-NMMA) and L-N omega-iminoethyl-L-ornithine (L-NIO).", "entity1": "eNOS", "entity2": "L-Nomega -monomethyl-L-arginine", "span1": [148, 152], "span2": [193, 224]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9780": {"label": 4, "data": {"text": "The sigma-receptor antagonist rimcazole (3 mg/kg, i.p.) inhibited the antitussive effect of dextromethorphan (30 mg/kg, i.p.", "entity1": "sigma-receptor", "entity2": "dextromethorphan", "span1": [4, 18], "span2": [92, 108]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11897": {"label": 8, "data": {"text": "Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acids to form epoxyeicosatrienoic acids (EETs), which possess various beneficial effects on the cardiovascular system.", "entity1": "Cytochrome P450 epoxygenase 2J2", "entity2": "epoxyeicosatrienoic acids", "span1": [0, 31], "span2": [79, 104]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14593": {"label": 3, "data": {"text": "In addition, 17-AAG treatment reduced cell viability, CDK2, CDK4, cyclin E, cyclin D1, and phosphorylated Rb levels in AhR-expressing lung AD cells.", "entity1": "cyclin E", "entity2": "17-AAG", "span1": [66, 74], "span2": [13, 19]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10300": {"label": 3, "data": {"text": "This approach is validated by the clinical efficacy and safety of sildenafil, the pioneering drug for selective PDE5 inhibitor therapy for ED.", "entity1": "PDE5", "entity2": "sildenafil", "span1": [112, 116], "span2": [66, 76]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3408": {"label": 3, "data": {"text": "However, phosphorylation of the p65/RelA subunit was clearly inhibited by PSE in stimulated cells.", "entity1": "p65", "entity2": "PSE", "span1": [32, 35], "span2": [74, 77]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3836": {"label": 3, "data": {"text": "Taken together, the data provide evidence that the synergistic antiproliferative effect of resveratrol and clofarabine is linked to the inhibition of Akt and Sp1 activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma.", "entity1": "Akt", "entity2": "clofarabine", "span1": [150, 153], "span2": [107, 118]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14999": {"label": 2, "data": {"text": "In monocytes, both EPA and DHA increased interleukin (IL)-10 without affecting tumor necrosis factor (TNF)-\u03b1 and IL-6.", "entity1": "interleukin (IL)-10", "entity2": "EPA", "span1": [41, 60], "span2": [19, 22]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15635": {"label": 3, "data": {"text": "In conclusion, nobiletin attenuates HGF-induced HepG2 cells metastasis involving both ERK and PI3K/Akt pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma.", "entity1": "PI3K", "entity2": "nobiletin", "span1": [94, 98], "span2": [15, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10669": {"label": 3, "data": {"text": "Especially, the compound 1 showed strong inhibition (IC50=1.33 microM) against the enzyme tyrosinase, as compared to the standard tyrosinase inhibitors kojic acid (IC50=16.67 microM) and L-mimosine (IC50=3.68 microM), indicating its potential used for the treatment of hyperpigmentation associated with the high production of melanocytes.", "entity1": "tyrosinase", "entity2": "L-mimosine", "span1": [90, 100], "span2": [187, 197]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"3925": {"label": 0, "data": {"text": "We have identified >50 potential IAP substrates of both cytosolic and mitochondrial origin that bear hallmark N-terminal IAP binding motifs.", "entity1": "IAP", "entity2": "N", "span1": [121, 124], "span2": [110, 111]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"15959": {"label": 1, "data": {"text": "4-Hydroxytamoxifen-stimulated processing of cyclin E is mediated via G protein-coupled receptor 30 (GPR30) and accompanied by enhanced migration in MCF-7 breast cancer cells.", "entity1": "GPR30)", "entity2": "4-Hydroxytamoxifen", "span1": [100, 106], "span2": [0, 18]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8922": {"label": 3, "data": {"text": "Carvedilol (0.3 mg/kg, iv) produced a significant inhibition of the beta 1 adrenoceptor mediated positive chronotropic response to isoproterenol.", "entity1": "beta 1 adrenoceptor", "entity2": "Carvedilol", "span1": [68, 87], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 9]},
	"9415": {"label": 4, "data": {"text": "This study was designed to determine the gastroprotective properties of cinitapride (CNT), a novel prokinetic benzamide derivative agonist of 5-HT4 and 5-HT1 receptors and 5-HT2 antagonist, on mucosal injury produced by 50% (v/v) ethanol.", "entity1": "5-HT4", "entity2": "CNT", "span1": [142, 147], "span2": [85, 88]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"10324": {"label": 2, "data": {"text": "Resiquimod-stimulated pDC also produce a number of other cytokines including TNF-alpha and IP-10.", "entity1": "cytokines", "entity2": "Resiquimod", "span1": [57, 66], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"1921": {"label": 8, "data": {"text": "The M564G mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, acetyl-CoA.", "entity1": "CrAT", "entity2": "acetyl-CoA", "span1": [155, 159], "span2": [210, 220]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"983": {"label": 2, "data": {"text": "Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and activating protein-1, which were increased in fructose-fed rats.", "entity1": "activating protein-1", "entity2": "fructose", "span1": [229, 249], "span2": [33, 41]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1420": {"label": 3, "data": {"text": "We hypothesized that the HED compounds would be most potent at the norepinephrine transporter (NET) compared to the serotonin or dopamine transporters and that the 1R diastereomers would be more effective than 1S diastereomers.", "entity1": "NET", "entity2": "HED", "span1": [95, 98], "span2": [25, 28]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"14931": {"label": 1, "data": {"text": "Moreover, selective estrogen response modulators (SERMs) with diverse structures also regulate transcription of ER\u03b1 and ER\u03b2.", "entity1": "ER\u03b2", "entity2": "estrogen", "span1": [120, 123], "span2": [20, 28]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8432": {"label": 1, "data": {"text": "The endogenous steroid lithocholic acid (LCA) dilates cerebral arteries via BK channel activation, which requires recognition by a BK \u03b21 site that includes Thr169.", "entity1": "BK \u03b21", "entity2": "lithocholic acid", "span1": [131, 136], "span2": [23, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12674": {"label": 1, "data": {"text": "The anti-emetic and pharmacological profile of AS-8112 ((R)-5-bromo-N-(1-ethyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-2-methoxy-6-methy lamino-3-pyridinecarboxamide.2 fumarate), a novel and potent dopamine D2, D3 and 5-hydroxytryptamine-3 (5-HT3) receptors ligand, was investigated in the present study.", "entity1": "5-hydroxytryptamine-3 (5-HT3) receptors", "entity2": "(R)-5-bromo-N-(1-ethyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-2-methoxy-6-methy lamino-3-pyridinecarboxamide.2 fumarate", "span1": [218, 257], "span2": [56, 176]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"565": {"label": 1, "data": {"text": "Previously, we reported that a primary heparin or heparan sulfate binding site resides in a distinct sequence in immunoglobulin (Ig)-like module II of the three modules of FGFR.", "entity1": "immunoglobulin (Ig)-like module II", "entity2": "sulfate", "span1": [113, 147], "span2": [58, 65]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1825": {"label": 8, "data": {"text": "QR2 catalyzes the two-electron reduction of menadione via the oxidation of N-alkylated or N-ribosylated nicotinamides.", "entity1": "QR2", "entity2": "N-ribosylated nicotinamides", "span1": [0, 3], "span2": [90, 117]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"7662": {"label": 3, "data": {"text": "We investigated the effect of captopril, an ACE inhibitor, on MMP-2 and MMP-9 in monocrotaline-induced right ventricular hypertrophy.", "entity1": "ACE", "entity2": "captopril", "span1": [44, 47], "span2": [30, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4927": {"label": 2, "data": {"text": "Compared with DM8W group, SOD and ALDH2 in EtOH+DM8W group was increased, MDA was decreased.", "entity1": "SOD", "entity2": "EtOH", "span1": [26, 29], "span2": [43, 47]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2332": {"label": 3, "data": {"text": "Multiple exposure to theophylline, a phosphodiesterase (PDE) inhibitor, induces acinar hypertrophy in the salivary gland.", "entity1": "PDE", "entity2": "theophylline", "span1": [56, 59], "span2": [21, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3184": {"label": 2, "data": {"text": "The maximum stimulation of Cdx2 and MUC2 mRNA induced by CDCA was observed at 3 h and by 6 h, respectively.", "entity1": "MUC2", "entity2": "CDCA", "span1": [36, 40], "span2": [57, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1646": {"label": 4, "data": {"text": "2-Amino-3-[3-hydroxy-5-(2-thiazolyl)-4-isoxazolyl]propionic acid (1) is a potent AMPA receptor agonist with moderate affinity for native kainic acid (KA) receptors, whereas (S)-E-4-(2,2-dimethylpropylidene)glutamic acid (3) show high affinity for the GluR5 subtype of KA receptors and much lower affinity for the GluR2 subtype of AMPA receptors.", "entity1": "AMPA receptor", "entity2": "2-Amino-3-[3-hydroxy-5-(2-thiazolyl)-4-isoxazolyl]propionic acid", "span1": [81, 94], "span2": [0, 64]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5942": {"label": 3, "data": {"text": "Trilostane, epostane and cyanoketone are potent inhibitors of 3 beta-HSD with Ki values of approximately 50 nM.", "entity1": "3 beta-HSD", "entity2": "cyanoketone", "span1": [62, 72], "span2": [25, 36]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12821": {"label": 1, "data": {"text": "It could also aid in the design of roscovitine derivatives displaying strict selectivity for either PDXK or CDKs.", "entity1": "CDKs", "entity2": "roscovitine", "span1": [108, 112], "span2": [35, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"932": {"label": 3, "data": {"text": "5-Fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of thymidylate synthase (TS).", "entity1": "thymidylate synthase", "entity2": "5-fluoro-2'-deoxyuridine", "span1": [216, 236], "span2": [23, 47]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4114": {"label": 3, "data": {"text": "Synthesis, molecular modeling and evaluation of novel N'-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone derivatives as dual inhibitors for cholinesterases and A\u03b2 aggregation.", "entity1": "A\u03b2", "entity2": "N'-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone", "span1": [163, 165], "span2": [54, 107]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13120": {"label": 2, "data": {"text": "SK-Br3 cells cultured in the presence of topoisomerase IIalpha (TOP2A) inhibitors doxorubicin and etopoxide (VP-16) demonstrated a 2- to 3-fold increase in FAS promoter activity when compared with control cells growing in drug-free culture conditions.", "entity1": "FAS promoter", "entity2": "VP-16", "span1": [156, 168], "span2": [109, 114]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"314": {"label": 5, "data": {"text": "The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM).", "entity1": "5-HT1A", "entity2": "spiroxatrine", "span1": [230, 236], "span2": [257, 269]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"4069": {"label": 2, "data": {"text": "Cortisol and IFNT stimulated endometrial HSD11B1 expression and activity, increased endometrial PTGS2 activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium.", "entity1": "HSD11B1", "entity2": "Cortisol", "span1": [41, 48], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6478": {"label": 8, "data": {"text": "Carbonic anhydrase (CA) is a zinc enzyme that catalyses the reversible hydration reaction of CO2 and plays a major role in the acid-base balance.", "entity1": "CA", "entity2": "CO2", "span1": [20, 22], "span2": [93, 96]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"10264": {"label": 8, "data": {"text": "Reuptake of extracellular noradrenaline (NA) into superior cervical ganglion (SCG) neurones is mediated by means of the noradrenaline transporter (NAT, uptake 1).", "entity1": "noradrenaline transporter", "entity2": "noradrenaline", "span1": [120, 145], "span2": [26, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"12635": {"label": 1, "data": {"text": "We expressed cardiac or smooth muscle alpha1C subunits in combination with beta2a and alpha2/delta subunits in human embryonic kidney cells, and used 2 mM Ca2+ as the permeant ion.", "entity1": "smooth muscle alpha1C", "entity2": "Ca2+", "span1": [24, 45], "span2": [155, 159]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6969": {"label": 1, "data": {"text": "As CRABPI was elevated far more than any other genes, we observed that the retinoids, all-trans retinoic acid and 9-cis retinoic acid, that bind CRABPI, promoted nitroblue tetrazolium-associated functional cell differentiation in p75NTR PC-3 cells, but not in neo control PC-3 cells.", "entity1": "p75NTR", "entity2": "9-cis retinoic acid", "span1": [230, 236], "span2": [114, 133]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"12937": {"label": 8, "data": {"text": "L-arg is converted to urea by arginase I in the liver and arginase II in the kidney.", "entity1": "arginase I", "entity2": "urea", "span1": [30, 40], "span2": [22, 26]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1]},
	"6444": {"label": 2, "data": {"text": "This study demonstrates that CB1093 and clenbuterol stimulate NGF levels in vitro and that AP-1 binding could be a commonality between the mechanism of NGF induction of these two compounds.", "entity1": "NGF", "entity2": "clenbuterol", "span1": [62, 65], "span2": [40, 51]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13900": {"label": 3, "data": {"text": "CONCLUSION: ACE inhibitors, such as captopril, may be applied as important compounds for MMP-2 inhibition in inflammation caused by CAPD.", "entity1": "ACE", "entity2": "captopril", "span1": [12, 15], "span2": [36, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15889": {"label": 8, "data": {"text": "Targeted disruption of the gene encoding the N-glycosyltransferase, prlH, abolished pyralomicin production, and recombinant expression of PrlA confirms the activity of this enzyme as a sugar phosphate cyclase involved in the formation of the C7-cyclitol moiety.", "entity1": "PrlA", "entity2": "C7", "span1": [138, 142], "span2": [242, 244]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"14023": {"label": 3, "data": {"text": "Inhibition of the NF-kappaB pathway was responsible for this effect since the colchicoside inhibited RANKL-induced NF-kappaB activation, activation of IkappaB kinase (IKK) and suppressed inhibitor of NF-kappaBalpha (IkappaBalpha) phosphorylation and degradation, an inhibitor of NF-kappaB.", "entity1": "IkappaBalpha", "entity2": "colchicoside", "span1": [216, 228], "span2": [78, 90]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9492": {"label": 3, "data": {"text": "Monoamine uptake inhibitors structurally analogous to cocaine (cocaethylene, CFT, betaCIT, CPT, (+)-cocaine, norcocaine, and benztropine) also produced this rapid pressor response, whereas structurally unrelated uptake inhibitors with diverse monoamine transporter selectivities (BTCP, indatraline, GBR 12935, mazindol, nomifensine, and zimeldine) either did not produce a rapid pressor response or produced only a small pressor response.", "entity1": "monoamine transporter", "entity2": "mazindol", "span1": [243, 264], "span2": [310, 318]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, 8, -1, 9]},
	"13404": {"label": 2, "data": {"text": "In the current project, we found that the selective H(1) antagonist pyrilamine also reversed the dizocilpine-induced impairment in PPI of tactile startle with an auditory prepulse.", "entity1": "H(1)", "entity2": "dizocilpine", "span1": [52, 56], "span2": [97, 108]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8072": {"label": 3, "data": {"text": "Contrary to the hypothesis, orlistat at 1 nM inhibited CES2 activity by 75% but no inhibition on CES1, placing CES2 one of the most sensitive targets of orlistat.", "entity1": "CES2", "entity2": "orlistat", "span1": [111, 115], "span2": [153, 161]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5562": {"label": 3, "data": {"text": "Treatment of cells with BCNU to inhibit glutathione reductase (GR) enhanced the CpG-induced intracellular oxidation and decreased the GSH/GSSG, with increased activation of NF-kappaB and a doubling in the CpG-induced production of IL-6 and TNF-alpha.", "entity1": "TNF-alpha", "entity2": "GSH", "span1": [240, 249], "span2": [134, 137]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, 2, -1, -1, -1, 3, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"9401": {"label": 1, "data": {"text": "Binding and transactivation assays were used to compare affinities and transcriptional activities of adapalene and tretinoin for the nuclear transcription factors, retinoic acid receptors (RARs).", "entity1": "nuclear transcription factors", "entity2": "tretinoin", "span1": [133, 162], "span2": [115, 124]}, "weak_labels": [-1, -1, -1, 1, -1, 1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11560": {"label": 0, "data": {"text": "We have expressed and characterized recombinant, N-terminally His-tagged human adenine phosphoribosyltransferase.", "entity1": "human adenine phosphoribosyltransferase", "entity2": "N", "span1": [73, 112], "span2": [49, 50]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5880": {"label": 1, "data": {"text": "Labetalol and the enantiomers lacked affinity at alpha 2-adrenoceptors while at alpha 1-adrenoceptors the order of potency was prazosin much greater than RR-SR greater than labetalol.", "entity1": "alpha 1-adrenoceptors", "entity2": "prazosin", "span1": [80, 101], "span2": [127, 135]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12324": {"label": 2, "data": {"text": "Ribavirin also enhanced recruitment of CDK9 (cyclin-dependent kinase 9) and AFF4 to F7.", "entity1": "F7", "entity2": "Ribavirin", "span1": [84, 86], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2079": {"label": 3, "data": {"text": "Synergistic cytotoxicity was demonstrated, and pemetrexed significantly decreased the amount of phosphorylated Akt, enhanced apoptosis, and increased the expression of dCK in A549 and Calu-6 cells, as well as the expression of the human nucleoside equilibrative transporter 1 (hENT1) in all cell lines.", "entity1": "phosphorylated Akt", "entity2": "pemetrexed", "span1": [96, 114], "span2": [47, 57]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"5457": {"label": 2, "data": {"text": "TSA selectively induced uc002mbe.2 in four studied HCC cell lines.", "entity1": "uc002mbe.2", "entity2": "TSA", "span1": [24, 34], "span2": [0, 3]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3246": {"label": 1, "data": {"text": "The rates of hAR transport for the exogenous steroids methyltrienelone (MET), nandrolone (NAN), and oxandrolone (OXA) are lower than that of testosterone and similar to those of the endogenous steroids ANE and DHT.", "entity1": "hAR", "entity2": "steroids", "span1": [13, 16], "span2": [193, 201]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"2723": {"label": 1, "data": {"text": "To determine the role of 14-3-3 in colorectal cancer apoptosis induced by nonsteroidal anti-inflammatory drugs (NSAIDs), we evaluated the effects of sulindac on 14-3-3epsilon protein expression in colorectal cancer cells.", "entity1": "14-3-3epsilon protein", "entity2": "sulindac", "span1": [161, 182], "span2": [149, 157]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15680": {"label": 0, "data": {"text": "Treatment with EVn-50 or VB1 resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of Histone 3 at Ser10, phosphorylation of Cdk1 at Tyr15, expression of cyclin B1, and decreased expression of Cdc25c.", "entity1": "Cdk1", "entity2": "Tyr", "span1": [216, 220], "span2": [224, 227]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11926": {"label": 1, "data": {"text": "Oxysterols interfere with ERK, hedgehog and wnt pathways of proliferation and differentiation.", "entity1": "wnt", "entity2": "Oxysterols", "span1": [44, 47], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8649": {"label": 3, "data": {"text": "Conversely, ovarian PRA and PRB were positively regulated by ethanol and ethanol-melatonin combination, whereas PRA was down-regulated in the uterus and oviduct after ethanol consumption.", "entity1": "PRA", "entity2": "ethanol", "span1": [112, 115], "span2": [167, 174]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1]},
	"2479": {"label": 1, "data": {"text": "Fingolimod (FTY720), a synthetic sphingosine phosphate receptor modulator that reduces the recirculation of lymphocytes to blood and peripheral tissues including inflammatory lesions and graft sites is undergoing phase III trials.", "entity1": "sphingosine phosphate receptor", "entity2": "Fingolimod", "span1": [33, 63], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"45": {"label": 3, "data": {"text": "Before the next drug intake, MAO-A inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with moclobemide but not with toloxatone.", "entity1": "MAO-A", "entity2": "moclobemide", "span1": [29, 34], "span2": [149, 160]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9513": {"label": 5, "data": {"text": "The present study describes the characterization of the binding properties and autoradiographic distribution of a new nonpeptide antagonist of neurotensin receptors, [3H]SR 142948A (2-[[5-(2,6-dimethoxyphenyl)-1-(4-(N-(3-dimethylaminopropyl)-N-methyl carbamoyl)-2-isopropylphenyl)-1H-pyrazole-3-carbonyl]-amino]-ad amantane-2-carboxylic acid, hydrochloride), in the rat brain.", "entity1": "neurotensin receptors", "entity2": "[3H]SR 142948A", "span1": [143, 164], "span2": [166, 180]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8772": {"label": 9, "data": {"text": "Overexpression of Akt1 or Akt2 in TW2.6 cells rescued growth inhibition caused by CAPE treatment.", "entity1": "Akt1", "entity2": "CAPE", "span1": [18, 22], "span2": [82, 86]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10748": {"label": 3, "data": {"text": "Clinical studies in cancer patients treated with the new fluoropyrimidine analogue capecitabine (N4-pentoxycarbonyl-5'-5-fluorocytidine) have shown that plasma 2'-deoxyuridine was significantly elevated after 1 week of treatment, consistent with inhibition of thymidylate synthase (TS).", "entity1": "TS", "entity2": "capecitabine", "span1": [282, 284], "span2": [83, 95]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1401": {"label": 3, "data": {"text": "These results suggest that gemfibrozil inhibits the induction of iNOS probably by inhibiting the activation of NF-kappaB, AP-1, and C/EBPbeta and that gemfibrozil, a prescribed drug for humans, may further find its therapeutic use in neuroinflammatory diseases.", "entity1": "iNOS", "entity2": "gemfibrozil", "span1": [65, 69], "span2": [27, 38]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6189": {"label": 5, "data": {"text": "These data indicate that mixed 5-HT1/5-HT2 receptor antagonists such as pizotifen and methysergide, and mixed 5-HT and catecholamine antagonists such as mianserin and mirtazapine are more potent antagonists of mCPP-induced behavioural inhibition in rats than the more selective 5-HT2A/5-HT2C antagonist ritanserin.", "entity1": "5-HT2", "entity2": "pizotifen", "span1": [37, 42], "span2": [72, 81]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"197": {"label": 0, "data": {"text": "Deduced amino acid sequence from the bovine oxytocin-neurophysin I precursor cDNA.", "entity1": "bovine oxytocin-neurophysin I precursor", "entity2": "amino acid", "span1": [37, 76], "span2": [8, 18]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1240": {"label": 3, "data": {"text": "Amrinone and milrinone, selective PDE3 inhibitors, suppressed TNF secretion to a lesser extent.", "entity1": "TNF", "entity2": "Amrinone", "span1": [62, 65], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7404": {"label": 1, "data": {"text": "These data support the novel finding that clofibrate treatment does not directly regulate BAT activity but does alter the subcellular localization of BAT.", "entity1": "BAT", "entity2": "clofibrate", "span1": [90, 93], "span2": [42, 52]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1164": {"label": 1, "data": {"text": "Binding experiments on mitiglinide, nateglinide, and repaglinide to SUR1 expressed in COS-1 cells revealed that they inhibit the binding of [3H]glibenclamide to SUR1 (IC50 values: mitiglinide, 280 nM; nateglinide, 8 microM; repaglinide, 1.6 microM), suggesting that they all share a glibenclamide binding site.", "entity1": "SUR1", "entity2": "nateglinide", "span1": [68, 72], "span2": [36, 47]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13035": {"label": 8, "data": {"text": "11Beta-HSD1 activates cortisone to cortisol to facilitate glucocorticoid receptor (GR)-mediated action.", "entity1": "11Beta-HSD1", "entity2": "cortisone", "span1": [0, 11], "span2": [22, 31]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5962": {"label": 3, "data": {"text": "Ambenonium was a less potent antagonist of tissue responses to acetylcholine, and the underestimation in the pKB (as compared to that obtained with bethanechol) could be eliminated by prior treatment of tissues with the acetylcholinesterase inhibitor neostigmine.", "entity1": "acetylcholinesterase", "entity2": "neostigmine", "span1": [220, 240], "span2": [251, 262]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14763": {"label": 3, "data": {"text": "Moreover, jaceosidin treatment resulted in phosphorylation of ERK, and pretreatment with the ERK inhibitor, PD98059, attenuated cell growth inhibition by jaceosidin.", "entity1": "ERK", "entity2": "PD98059", "span1": [93, 96], "span2": [108, 115]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8110": {"label": 3, "data": {"text": "These results suggested that wogonin could inhibit H2O2-induced vascular permeability by downregulating the phosphorylation of cav-1, and that it might have a therapeutic potential for the diseases associated with the development of both oxidant and vascular permeability.", "entity1": "cav-1", "entity2": "wogonin", "span1": [127, 132], "span2": [29, 36]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6678": {"label": 1, "data": {"text": "or were chronically pretreated with the selective beta(2)-adrenoceptor agonist salbutamol (40 microg/kg/h) for 1 week to induce beta(2)-adrenoceptor desensitization.", "entity1": "beta(2)-adrenoceptor", "entity2": "salbutamol", "span1": [128, 148], "span2": [79, 89]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1429": {"label": 3, "data": {"text": "They included the COX-1 inhibitor indomethacin; the COX-2 inhibitor NS-398; the mixed COX-1/COX-2 inhibitor ibuprofen; the nitric oxide (NO) derivatives of indomethacin, ibuprofen and flurbiprofen; the 5-LOX inhibitor REV 5901; and the 5-LOX activating protein (FLAP) inhibitor MK-886.", "entity1": "5-LOX activating protein", "entity2": "MK-886", "span1": [236, 260], "span2": [278, 284]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12894": {"label": 2, "data": {"text": "Both H(2)S solution prepared by bubbling pure H(2)S gas and NaSH, a H(2)S donor, dose dependently induced HO-1 expression through the activation of the extracellular signal-regulated kinase (ERK).", "entity1": "extracellular signal-regulated kinase", "entity2": "H(2)S", "span1": [152, 189], "span2": [5, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12812": {"label": 2, "data": {"text": "Treatment with carvedilol reversed both protein and mRNA of HIF-1alpha, VEGF, BNP, and NGF-beta to the baseline values.", "entity1": "NGF-beta", "entity2": "carvedilol", "span1": [87, 95], "span2": [15, 25]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9505": {"label": 1, "data": {"text": "In conclusion, these findings indicate that [3H]SR 142948A is a new potent antagonist radioligand which recognizes with high affinity both neurotensin NT1 and NT2 receptors and represents thus an excellent tool to study neurotensin receptors in the rat brain.", "entity1": "neurotensin NT1", "entity2": "[3H]SR 142948A", "span1": [139, 154], "span2": [44, 58]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7114": {"label": 5, "data": {"text": "Tamoxifen blocks the action of estrogen by binding to the ER, and possesses both ER-agonist and antagonist properties.", "entity1": "ER", "entity2": "Tamoxifen", "span1": [81, 83], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7357": {"label": 1, "data": {"text": "We also found that 17beta-estradiol protects dopamine neurons from injury induced by the complex I inhibitor, 1-methyl-4-phenyl pyridinium (MPP(+)) in a time- and ER-dependent manner.", "entity1": "ER", "entity2": "17beta-estradiol", "span1": [163, 165], "span2": [19, 35]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11209": {"label": 3, "data": {"text": "Block of erg3 by sertindole also displayed a positive voltage-dependence.", "entity1": "erg3", "entity2": "sertindole", "span1": [9, 13], "span2": [17, 27]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9058": {"label": 1, "data": {"text": "7-Hydroxy levomepromazine, 3-hydroxy levomepromazine and 7-hydroxy fluphenazine had only 10% of the potency of the parent drug in histamine H1 receptor binding, while the 7-hydroxy-metabolites of chlorpromazine and perphenazine had about 75% of the potency of the parent drug in this binding system.", "entity1": "histamine H1 receptor", "entity2": "3-hydroxy levomepromazine", "span1": [130, 151], "span2": [27, 52]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13439": {"label": 8, "data": {"text": "TGF-beta1 and high D-glucose increased hCAT-1 mRNA expression ( approximately 8-fold) and maximal transport velocity (V(max)), L-[(3)H]citrulline formation from L-[(3)H]arginine (index of NO synthesis) and endothelial NO synthase (eNOS) protein abundance, but did not alter eNOS phosphorylation.", "entity1": "eNOS", "entity2": "NO", "span1": [231, 235], "span2": [188, 190]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, 9]},
	"14067": {"label": 1, "data": {"text": "These findings support the notion that glucose shortage-induced apoptosis, specific of K-ras-transformed cells, is associated to a derangement of PKA signaling that leads to mitochondrial complex I decrease, reduction of ATP formation, prevalence of mitochondrial fission over fusion, and thereby opening new approaches for development of anticancer drugs.", "entity1": "K-ras", "entity2": "glucose", "span1": [87, 92], "span2": [39, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"10882": {"label": 3, "data": {"text": "Irinotecan (CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) has exhibited clinical activities against a broad spectrum of carcinomas by inhibiting DNA topoisomerase I (Topo I).", "entity1": "Topo I", "entity2": "CPT-11", "span1": [196, 202], "span2": [12, 18]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"10991": {"label": 3, "data": {"text": "Tyrosine kinase inhibitors are quinazoline-derived, low molecular weight synthetic molecules that can block the intracellular tyrosine kinase domain of several receptors, including EGFR, Erb2, and vascular endothelial growth factor receptor, and thereby inhibit ligand-induced receptor phosphorylation and abrogate the biologic effect of EGFR signaling.", "entity1": "tyrosine kinase domain", "entity2": "quinazoline", "span1": [126, 148], "span2": [31, 42]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5337": {"label": 3, "data": {"text": "No effects were observed when fenclozic acid was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major human cytochrome P450 enzymes, inhibition of the biliary efflux transporters BSEP and MRP2 or mitochondrial toxicity to THLE or HepG2 cells.", "entity1": "MRP2", "entity2": "fenclozic acid", "span1": [257, 261], "span2": [30, 44]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"4527": {"label": 8, "data": {"text": "Carboxylesterases hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively.", "entity1": "Carboxylesterases", "entity2": "thioesters", "span1": [0, 17], "span2": [48, 58]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"2869": {"label": 2, "data": {"text": "Recently, it has been shown that the activation of particular T2R bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and acesulfame-K.", "entity1": "T2R", "entity2": "acesulfame-K", "span1": [62, 65], "span2": [165, 177]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1575": {"label": 3, "data": {"text": "The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "entity1": "AChE", "entity2": "[1,8]naphthyridines", "span1": [26, 30], "span2": [135, 154]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15458": {"label": 3, "data": {"text": "Based on our previously published work on CXCR4 antagonists, we have synthesized a series of aryl sulfonamides that inhibit the CXCR4/CXCL12 interaction.", "entity1": "CXCL12", "entity2": "aryl sulfonamides", "span1": [134, 140], "span2": [93, 110]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2927": {"label": 8, "data": {"text": "The Na(+)/Ca(2+) exchanger (NCX) is a bidirectional transporter that normally extrudes Ca(2+) from the cell (forward mode), but also brings Ca(2+) into the cell (reverse mode) under special conditions such as intracellular Na(+) (Na(+)(i)) accumulation or membrane depolarization.", "entity1": "Na(+)/Ca(2+) exchanger", "entity2": "Ca(2+)", "span1": [4, 26], "span2": [87, 93]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"13374": {"label": 8, "data": {"text": "Several genes involved with steroid metabolism also showed remarkable expression changes, including increased expression of 17beta-hydroxysteroid dehydrogenase-7 (HSD17beta7; involved in estradiol production) and decreased expression of HSD17beta5 (involved in testosterone production).", "entity1": "17beta-hydroxysteroid dehydrogenase-7", "entity2": "estradiol", "span1": [124, 161], "span2": [187, 196]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"10983": {"label": 3, "data": {"text": "Preincubation (30 min) of bovine tracheal smooth muscle with various concentrations (0.1, 1 and 10 microM) of fenoterol decreased isoprenaline-induced maximal relaxation (E(max)) of methacholine-contracted preparations in a concentration dependent fashion, indicating desensitization of the beta(2)-adrenoceptor.", "entity1": "beta(2)-adrenoceptor", "entity2": "fenoterol", "span1": [291, 311], "span2": [110, 119]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"15991": {"label": 1, "data": {"text": "Here we show that puerarin increases proliferation and differentiation and opposes cisplatin-induced apoptosis in human osteoblastic MG-63 cells containing two estrogen receptor (ER) isoforms.", "entity1": "estrogen receptor", "entity2": "cisplatin", "span1": [160, 177], "span2": [83, 92]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6227": {"label": 1, "data": {"text": "Kinetic studies comparing the binding of [3H]eletriptan and [3H]sumatriptan to the human recombinant 5-HT1B and 5-HT1D receptors expressed in HeLa cells revealed that both radioligands bound with high specificity (>90%) and reached equilibrium within 10-15 min.", "entity1": "human recombinant 5-HT1B", "entity2": "[3H]eletriptan", "span1": [83, 107], "span2": [41, 55]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3320": {"label": 1, "data": {"text": "VP-16 induced the release of IL-8, and addition of MXF reduced enhanced release and the spontaneous release of VEGF from the cells.", "entity1": "IL-8", "entity2": "MXF", "span1": [29, 33], "span2": [51, 54]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1039": {"label": 5, "data": {"text": "Clinical effects of pranlukast, an oral leukotriene receptor antagonist, in mild-to-moderate asthma: a 4 week randomized multicentre controlled trial.", "entity1": "leukotriene receptor", "entity2": "pranlukast", "span1": [40, 60], "span2": [20, 30]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9090": {"label": 9, "data": {"text": "In contrast to diethylcarbamazine, piriprost (U-60,257; 6,9-deepoxy-6,9-(phenylimino)-delta 6,8-prostaglandin I1), which inhibits the formation of sulfidopeptide leuktrienes in RBL cells at the 5-lipoxygenase step (EC50 5 microM), did not inhibit the leukotriene synthetase of these cells.", "entity1": "leukotriene synthetase", "entity2": "U-60,257", "span1": [251, 273], "span2": [46, 54]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9691": {"label": 1, "data": {"text": "Pretreatment with the 5-HT1A antagonist WAY-100,635 (10 micrograms/kg i.v.) prevented the ziprasidone-induced inhibition; the same dose of WAY-100,635 had little effect on the inhibition produced by clozapine and olanzapine.", "entity1": "5-HT1A", "entity2": "ziprasidone", "span1": [22, 28], "span2": [90, 101]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"13652": {"label": 0, "data": {"text": "The distances between the protons H20 and H2, H18 and H2, and H18 and H4 are shorter following their binding to the PGIS in solution-down to within 5 A.", "entity1": "PGIS", "entity2": "H2", "span1": [116, 120], "span2": [42, 44]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13601": {"label": 5, "data": {"text": "Desvenlafaxine succinate identifies novel antagonist binding determinants in the human norepinephrine transporter.", "entity1": "human norepinephrine transporter", "entity2": "Desvenlafaxine succinate", "span1": [81, 113], "span2": [0, 24]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"3271": {"label": 1, "data": {"text": "To examine the interaction of S100A4 with TFP, we determined the 2.3 A crystal structure of human Ca(2+)-S100A4 bound to TFP.", "entity1": "S100A4", "entity2": "TFP", "span1": [30, 36], "span2": [42, 45]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13469": {"label": 8, "data": {"text": "Acetyl-coenzyme A carboxylase (ACC) enzymes exist as two isoforms, ACC1 and ACC2, which play critical roles in fatty acid biosynthesis and oxidation.", "entity1": "Acetyl-coenzyme A carboxylase", "entity2": "fatty acid", "span1": [0, 29], "span2": [111, 121]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6634": {"label": 5, "data": {"text": "Involvement of alpha(1)-adrenoceptors was established as mydriatic responses were inhibited by systemic administration of nonselective alpha-adrenoceptor antagonists, phentolamine (0.3-3 mg/kg) and phenoxybenzamine (0.03-0.3 mg/kg), as well as by the selective alpha(1)-adrenoceptor antagonist, prazosin (0.3 mg/kg).", "entity1": "alpha(1)-adrenoceptor", "entity2": "prazosin", "span1": [261, 282], "span2": [295, 303]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8578": {"label": 3, "data": {"text": "ATO inhibited the phosphorylation and activation of AKT and STAT3 through Notch signaling blockade.", "entity1": "STAT3", "entity2": "ATO", "span1": [60, 65], "span2": [0, 3]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"14010": {"label": 3, "data": {"text": "Cabozantinib (XL184) is a small-molecule kinase inhibitor with potent activity toward MET and VEGF receptor 2 (VEGFR2), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including RET, KIT, AXL, and FLT3.", "entity1": "FLT3", "entity2": "XL184", "span1": [258, 262], "span2": [14, 19]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7900": {"label": 1, "data": {"text": "TCDD acts through the aryl hydrocarbon receptor (AhR), which interacts with the androgen receptor (AR).", "entity1": "aryl hydrocarbon receptor", "entity2": "TCDD", "span1": [22, 47], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15176": {"label": 3, "data": {"text": "GnRH stimulation of CREB phosphorylation (pCREB) in the gonadotrope-derived L\u03b2T2 cell line was attenuated by a protein kinase A (PKA) inhibitor, H89.", "entity1": "pCREB", "entity2": "H89", "span1": [42, 47], "span2": [145, 148]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9942": {"label": 3, "data": {"text": "RESULTS: NF-kappaB/Rel activity induced by tumor necrosis factor alpha, 12-O-tetradecanoylphorbol-13-acetate, or overexpression of NF-kappaB-inducing kinase, IKK-alpha, IKK-beta, or constitutively active IKK-alpha and IKK-beta mutants was inhibited dose dependently by sulfasalazine.", "entity1": "IKK-alpha", "entity2": "sulfasalazine", "span1": [204, 213], "span2": [269, 282]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14986": {"label": 2, "data": {"text": "Additionally, these effects of ATO on \u03b3-H2AX, Chk1, Chk2, p53, and p21(waf1/cip1) were reduced by an ATM inhibitor.", "entity1": "H2AX", "entity2": "ATO", "span1": [40, 44], "span2": [31, 34]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2901": {"label": 4, "data": {"text": "OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting alpha2 adrenergic receptor (AR) agonist (dexmedetomidine).", "entity1": "AR", "entity2": "dexmedetomidine", "span1": [166, 168], "span2": [179, 194]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8764": {"label": 1, "data": {"text": "Molecular docking studies suggested that SB has a good affinity towards vinblastine-binding site on \u03b2-tubulin subunit.", "entity1": "\u03b2-tubulin", "entity2": "vinblastine", "span1": [100, 109], "span2": [72, 83]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5189": {"label": 2, "data": {"text": "Treatment of A549 and H1299 cells with dioscin caused a dose-dependent increase in ERK1/2 and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR.", "entity1": "ERK1/2", "entity2": "dioscin", "span1": [83, 89], "span2": [39, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7803": {"label": 1, "data": {"text": "However, 4'G-RSV, but not 3G-RSV, induced SIRT1-dependent histone H3 deacetylation and SOD2 expression in mouse C2C12 skeletal myoblasts; as with RSV, SIRT1 knockdown blunted these effects.", "entity1": "histone H3", "entity2": "4'G-RSV", "span1": [58, 68], "span2": [9, 16]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"2391": {"label": 0, "data": {"text": "The x-ray co-crystal structure of LeuRS showed that a C-terminal extension of about 60 amino acids forms a discrete domain, which is unique among the LeuRSs and interacts with the corner of the L-shaped tRNALeu.", "entity1": "LeuRSs", "entity2": "C", "span1": [150, 156], "span2": [54, 55]}, "weak_labels": [0, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4271": {"label": 2, "data": {"text": "Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, GSK3\u03b2 phosphorylation, cleaved PARP and deceased AEG-1 induced by ursolic acid in HepG2 cells.", "entity1": "GSK3\u03b2", "entity2": "ursolic acid", "span1": [69, 74], "span2": [135, 147]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13628": {"label": 0, "data": {"text": "We postulate that this conserved Gly residue provides a flexible hinge within the Top1p catalytic pocket to facilitate linker dynamics and the structural alterations that accompany drug binding of the covalent enzyme-DNA intermediate.", "entity1": "Top1p", "entity2": "Gly", "span1": [82, 87], "span2": [33, 36]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11915": {"label": 1, "data": {"text": "We studied accumulation of lipid metabolites [triglycerides (TAGs), diglycerides (DAGs)] and ceramides in relation to insulin signaling and expression and phosphorylation of PTP1B by preincubating rat skeletal muscle cells (L6 myotubes) with three saturated and three unsaturated free fatty acids (FFAs) (200 \u03bcM).", "entity1": "insulin", "entity2": "diglycerides", "span1": [118, 125], "span2": [68, 80]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6011": {"label": 3, "data": {"text": "CONCLUSIONS: Nabumetone does dose-dependently inhibit the cyclooxygenase activity of platelet PGHS-1 of healthy subjects both in vivo and ex vivo.", "entity1": "PGHS-1", "entity2": "Nabumetone", "span1": [94, 100], "span2": [13, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"125": {"label": 3, "data": {"text": "Again, inhibition of the actin-activated myosin Mg2+-ATPase and myosin filament assembly by felodipine and the p-chloro analogue could be reversed by raising the calmodulin concentration.", "entity1": "myosin", "entity2": "p-chloro", "span1": [41, 47], "span2": [111, 119]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2713": {"label": 2, "data": {"text": "There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the parathion-treated cells.", "entity1": "Ezrin", "entity2": "parathion", "span1": [79, 84], "span2": [140, 149]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1986": {"label": 3, "data": {"text": "In addition, inhibiting the binding of the fast inactivation lid (Nav1.5 ICM + MTSET) did not alter mibefradil block, confirming that the drug does not preferentially interact with the fast-inactivated state.", "entity1": "Nav1.5", "entity2": "mibefradil", "span1": [66, 72], "span2": [100, 110]}, "weak_labels": [-1, -1, -1, 1, 1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"15531": {"label": 1, "data": {"text": "DMN treatment for 4weeks led to marked liver fibrosis as assessed by serum biochemistry, histopathological examination, and hepatic lipid peroxidation and collagen content.", "entity1": "collagen", "entity2": "DMN", "span1": [155, 163], "span2": [0, 3]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12066": {"label": 1, "data": {"text": "The second part of this study consisted of looking for possible changes in central 5-HT receptors 24 h after either a single or a repeated (for 14 days) treatment with amoxapine (10 mg/kg i.p.", "entity1": "5-HT receptors", "entity2": "amoxapine", "span1": [83, 97], "span2": [168, 177]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13112": {"label": 8, "data": {"text": "We propose a model whereby compartmentalized PDEs, rather than representing an enzymatic barrier to cAMP diffusion, act as a sink to drain the second messenger from discrete locations, resulting in multiple and simultaneous domains with different cAMP concentrations irrespective of their distance from the site of cAMP synthesis.", "entity1": "PDEs", "entity2": "cAMP", "span1": [45, 49], "span2": [247, 251]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3899": {"label": 2, "data": {"text": "Ozone plus PM(2.5) exposure, however, induced CRP, IL-6, CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way.", "entity1": "CK", "entity2": "Ozone", "span1": [57, 59], "span2": [0, 5]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11533": {"label": 1, "data": {"text": "The objective of the study is to investigate whether dopamine D2 receptor occupancy by risperidone and plasma levels over time can account for therapeutic efficacy and the latency period to response.", "entity1": "dopamine D2 receptor", "entity2": "risperidone", "span1": [53, 73], "span2": [87, 98]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11379": {"label": 1, "data": {"text": "P2Y12, a new platelet ADP receptor, target of clopidogrel.", "entity1": "P2Y12", "entity2": "clopidogrel", "span1": [0, 5], "span2": [46, 57]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10352": {"label": 9, "data": {"text": "Unlike GW660511X, omapatrilat abolished the production of BrBK1-5 and BrBK1-7, suggesting a better ACE inhibition effect over GW660511X as no NEP activity was found.", "entity1": "BrBK1-7", "entity2": "GW660511X", "span1": [70, 77], "span2": [7, 16]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"9606": {"label": 9, "data": {"text": "Mutation in the Walker A and B motifs of NBF2 of SUR1 abolished this stabilizing effect of MgADP.", "entity1": "SUR1", "entity2": "MgADP", "span1": [49, 53], "span2": [91, 96]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5432": {"label": 3, "data": {"text": "A series of benzenesulfonamides incorporating cyanoacrylamide moieties (tyrphostine analogs) were assayed as inhibitors of the \u03b2-carbonic anhydrase (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA.", "entity1": "ScCA", "entity2": "benzenesulfonamides", "span1": [196, 200], "span2": [12, 31]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"963": {"label": 5, "data": {"text": "The antagonistic property of rilmenidine at human alpha(2A)-adrenoceptors indicates that in contrast to the suggestion based on rabbit data, the hypotensive property of the drug in humans is not due to activation of alpha(2A)-adrenoceptors but other, presumably I(1)-imidazoline receptors, are probably involved.", "entity1": "human alpha(2A)-adrenoceptors", "entity2": "rilmenidine", "span1": [44, 73], "span2": [29, 40]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"12454": {"label": 8, "data": {"text": "Cytochrome P450 2E1 (CYP 450 2E1), activity was determined as hydroxylation of aniline in liver microsomes.", "entity1": "CYP 450 2E1", "entity2": "aniline", "span1": [21, 32], "span2": [79, 86]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14631": {"label": 8, "data": {"text": "Gemcitabine (dFdC, 2',2'-difluorodeoxycytidine) is metabolized by cytidine deaminase (CDA) and deoxycytidine kinase (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.", "entity1": "deoxycytidine kinase", "entity2": "Gemcitabine", "span1": [95, 115], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12215": {"label": 1, "data": {"text": "This mechanism involves the calcium-dependent tyrosine kinase Pyk2, the non-receptor tyrosine kinase c-Src and the focal adhesion protein/steroid receptor co-factor, Hic-5.", "entity1": "Pyk2", "entity2": "calcium", "span1": [62, 66], "span2": [28, 35]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2615": {"label": 9, "data": {"text": "The activity of polymerases containing mutations known to confer resistance to foscarnet (V715M, T700A and N495K) was inhibited by concentrations of foscarnet eight to 14 times higher than those required to inhibit wild-type polymerases.", "entity1": "V715M", "entity2": "foscarnet", "span1": [90, 95], "span2": [79, 88]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"146": {"label": 1, "data": {"text": "These data demonstrate that loperamide differently modifies the stimulatory action of LVP and CRH on ACTH secretion: namely, LVP and loperamide act in an additive manner, while CRH and loperamide interact in a non additive way.", "entity1": "CRH", "entity2": "loperamide", "span1": [94, 97], "span2": [28, 38]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"446": {"label": 1, "data": {"text": "Epinastine (WAL 801CL) modulates the noncholinergic contraction in guinea-pig airways in vitro by a prejunctional 5-HT1-like receptor.", "entity1": "5-HT1-like receptor", "entity2": "WAL 801CL", "span1": [114, 133], "span2": [12, 21]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3481": {"label": 9, "data": {"text": "Swertiamarin treatment had no significant effect on adipogenesis, or the mRNA expression of PPAR-\u03b3 and GLUT-4; however, there was a significant increase in the mRNA expression of adiponectin.", "entity1": "PPAR-\u03b3", "entity2": "Swertiamarin", "span1": [92, 98], "span2": [0, 12]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13021": {"label": 8, "data": {"text": "It has been known for decades that lithium chloride (LiCl) leads to D-myo-inositol 1-phosphate accumulation on GPCR activation by inhibiting inositol monophosphatase, the final enzyme of the IP3 metabolic cascade.", "entity1": "inositol monophosphatase", "entity2": "IP3", "span1": [141, 165], "span2": [191, 194]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8153": {"label": 3, "data": {"text": "DPEP induced dose-dependent reduction of the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitant reduction in the production of NO and prostaglandin E(2) (PGE(2)).", "entity1": "COX-2", "entity2": "DPEP", "span1": [124, 129], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"15250": {"label": 1, "data": {"text": "Selective oxidation of \u03c9-tertiary amine self-assembled thiol monolayers to tertiary amine N-oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them.", "entity1": "lysozyme", "entity2": "tertiary amine N-oxides", "span1": [152, 160], "span2": [75, 98]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9743": {"label": 4, "data": {"text": "However, in contrast to the selective alpha(2)-AR antagonist, fluparoxan, the 5-HT(1A) agonist actions of yohimbine suppress 5-HT levels alone and underlie its inability to augment the influence of fluoxetine upon 5-HT levels.", "entity1": "5-HT(1A)", "entity2": "yohimbine", "span1": [78, 86], "span2": [106, 115]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7306": {"label": 8, "data": {"text": "Here, we describe a new photolabile alanine derivative based on protection of alanine with the 4-methoxy-7-nitroindolinyl (MNI) caging group, which we use for pre-steady-state kinetic analysis of alanine transport by ASCT2, SNAT1, and SNAT2.", "entity1": "ASCT2", "entity2": "alanine", "span1": [217, 222], "span2": [36, 43]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"10817": {"label": 9, "data": {"text": "Treatment with valsartan, doxazosin, or N-acetylcysteine did not significantly affect HIF-1alpha and VEGF proteins expression in the banding groups.", "entity1": "VEGF", "entity2": "valsartan", "span1": [101, 105], "span2": [15, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3859": {"label": 3, "data": {"text": "HSYA suppressed the expression of TLR-4, Myd88, ICAM-1, TNF\u03b1, IL-1\u03b2 and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.", "entity1": "Myd88", "entity2": "HSYA", "span1": [41, 46], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3721": {"label": 3, "data": {"text": "Furthermore, N-BPs decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and mTOR via suppression of Ras prenylation and enhanced Bim expression.", "entity1": "mTOR", "entity2": "BPs", "span1": [106, 110], "span2": [15, 18]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14960": {"label": 1, "data": {"text": "The peptide YR-11 (YLEIEFSLKHR), obtained by direct substitution of cysteine with a serine residue in the template sequence, significantly (p<0.05) inhibited RANK-RANKL binding, and RANKL induced TRAP activity and formation of multinucleated osteoclasts without any cytotoxicity.", "entity1": "RANK", "entity2": "YR-11", "span1": [158, 162], "span2": [12, 17]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5413": {"label": 1, "data": {"text": "In addition, ATM7 potentiates 3,4-methylenedioxy-N-methylamphetamine (MDMA, \"Ecstasy\")-induced reversed transport by SERT.", "entity1": "SERT", "entity2": "MDMA", "span1": [117, 121], "span2": [70, 74]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"10995": {"label": 0, "data": {"text": "The rabbit PAT1 cDNA was isolated (2296bp including both 5' and 3' untranslated regions and poly(A) tail) and the open reading frame codes for a protein of 475 amino acids (92% identity to human PAT1).", "entity1": "human PAT1", "entity2": "amino acids", "span1": [189, 199], "span2": [160, 171]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15201": {"label": 3, "data": {"text": "In HaCaT cells, buthanol and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-\u03b1 (TNF- \u03b1).", "entity1": "inducible nitric oxide synthase", "entity2": "buthanol", "span1": [296, 327], "span2": [16, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12911": {"label": 8, "data": {"text": "While either blockage of HO activity by the HO inhibitor, tin protoporphyrin IX, or down-regulation of HO-1 expression by HO-1 small interfering RNA (siRNA) reversed the inhibitory effects of H(2)S on iNOS expression and NO production, HO-1 overexpression produced the same inhibitory effects of H(2)S. In addition, LPS-induced nuclear factor (NF)-kappaB activation was diminished in RAW264.7 macrophages preincubated with H(2)S. Interestingly, the inhibitory effect of H(2)S on NF-kappaB activation was reversed by the transient transfection with HO-1 siRNA, but was mimicked by either HO-1 gene transfection or treatment with carbon monoxide (CO), an end product of HO-1.", "entity1": "HO-1", "entity2": "CO", "span1": [668, 672], "span2": [645, 647]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"8880": {"label": 1, "data": {"text": "The induction of IGFBP-4 protein was dependent on a functional aryl hydrocarbon receptor and was preceded by a rapid increase in the level of IGFBP-4 mRNA indicating that IGFBP-4 is a previously unknown transcriptional target of TCDD in 5L cells.", "entity1": "IGFBP-4", "entity2": "TCDD", "span1": [171, 178], "span2": [229, 233]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10461": {"label": 3, "data": {"text": "Blocking EGFR signaling with the EGFR/HER-2 kinase inhibitor (KI) GW572016 decreased the postradiation survival of irradiated Ras-transformed cells and normal cells but had no effect on the survival of unirradiated cells.", "entity1": "EGFR", "entity2": "GW572016", "span1": [9, 13], "span2": [66, 74]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14887": {"label": 2, "data": {"text": "Induction of HO-1 through p38 MAPK/Nrf2 signaling pathway by ethanol extract of Inula helenium L. reduces inflammation in LPS-activated RAW 264.7 cells and CLP-induced septic mice.", "entity1": "HO-1", "entity2": "ethanol", "span1": [13, 17], "span2": [61, 68]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2067": {"label": 3, "data": {"text": "In this study, using a model of gentamicin C (GMC)-induced reduction in SGLT1 activity, we examined whether ligands for megalin protect LLC-PK1 cells from the GMC-induced reduction in SGLT1 activity.", "entity1": "SGLT1", "entity2": "gentamicin C", "span1": [72, 77], "span2": [32, 44]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2411": {"label": 3, "data": {"text": "To determine whether arginases modulate the endothelial NO synthesis, we investigated the effects of the competitive arginase inhibitor N(omega)-hydroxy-nor-L-arginine (Nor-NOHA) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs).", "entity1": "arginase", "entity2": "N(omega)-hydroxy-nor-L-arginine", "span1": [117, 125], "span2": [136, 167]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, 6, -1, -1, -1, 8, -1, -1, -1, -1]},
	"2358": {"label": 3, "data": {"text": "Thus, sorafenib may inhibit tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of Raf and Kit signaling) and/or on tumor angiogenesis (through inhibition of VEGFR and PDGFR signaling).", "entity1": "PDGFR", "entity2": "sorafenib", "span1": [206, 211], "span2": [6, 15]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3138": {"label": 8, "data": {"text": "The present study examined the effect of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), on VMAT2 activity by measuring adenosine triphosphate-dependent [(3)H]dopamine uptake into synaptic vesicles prepared from rat striatum.", "entity1": "VMAT2", "entity2": "[(3)H]dopamine", "span1": [118, 123], "span2": [179, 193]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7760": {"label": 3, "data": {"text": "Rescue of this impaired extinction consolidation/retrieval was achieved with d-cycloserine (N-methly-d-aspartate partial agonist) or MS-275 (histone deacetylase (HDAC) inhibitor), applied after extinction training.", "entity1": "histone deacetylase", "entity2": "MS-275", "span1": [141, 160], "span2": [133, 139]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8365": {"label": 1, "data": {"text": "About 99% of a dose of diflunisal is unavailable for reaction with the target enzyme, because diflunisal strongly binds to human serum albumin (HSA).", "entity1": "HSA", "entity2": "diflunisal", "span1": [144, 147], "span2": [94, 104]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12439": {"label": 6, "data": {"text": "This Letter describes the further chemical optimization of the M5 PAM MLPCN probes ML129 and ML172.", "entity1": "M5", "entity2": "ML129", "span1": [63, 65], "span2": [83, 88]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3018": {"label": 2, "data": {"text": "Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2.", "entity1": "p21", "entity2": "Statins", "span1": [17, 20], "span2": [0, 7]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2222": {"label": 9, "data": {"text": "Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis.", "entity1": "D816V", "entity2": "imatinib", "span1": [35, 40], "span2": [45, 53]}, "weak_labels": [-1, -1, 0, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2991": {"label": 1, "data": {"text": "Catalytic-site affinities for cGMP, vardenafil, sildenafil, tadalafil, or 3-isobutyl-1-methylxanthine (IBMX) were respectively weakened 14-, 123-, 30-, 51-, and 43-fold for Y612A; 63-, 511-, 43-, 95- and 61-fold for Q817A; and 59-, 448-, 71-, 137-, and 93-fold for F820A.", "entity1": "Y612A", "entity2": "tadalafil", "span1": [173, 178], "span2": [60, 69]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6116": {"label": 3, "data": {"text": "Previous studies have resulted in the classification of amezinium as a selective inhibitor of neuronal monoamine oxidase (MAO), because it is a much more potent MAO inhibitor in intact tissues, in which it is accumulated in noradrenergic neurones by uptake1, than in tissue homogenates.", "entity1": "MAO", "entity2": "amezinium", "span1": [161, 164], "span2": [56, 65]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14288": {"label": 9, "data": {"text": "Valpromide (VPD), the amide derivative of VPA, does not inhibit HDAC activity and is a weak teratogen in vivo.", "entity1": "HDAC", "entity2": "VPD", "span1": [64, 68], "span2": [12, 15]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"821": {"label": 3, "data": {"text": "Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit HVA Ca2+ channels was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2.", "entity1": "HVA Ca2+ channels", "entity2": "thromboxane A2", "span1": [258, 275], "span2": [49, 63]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"425": {"label": 5, "data": {"text": "(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned human alpha 1D adrenoceptors.", "entity1": "human alpha 1D adrenoceptors", "entity2": "(+)-Tamsulosin", "span1": [258, 286], "span2": [0, 14]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3002": {"label": 1, "data": {"text": "The molecular bases for phosphodiesterase 5 (PDE5) catalytic-site affinity for cyclic guanosine monophosphate (cGMP) and potency of inhibitors are poorly understood.", "entity1": "PDE5", "entity2": "cGMP", "span1": [45, 49], "span2": [111, 115]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14530": {"label": 0, "data": {"text": "The serotonin (5-HT) receptors of type 6 (5-HT6) are quite different from all other 5-HT receptors, as they include a short third cytoplasmatic loop and a long C-terminal tail, and one intron located in the middle of the third cytoplasmatic loop.", "entity1": "5-HT6", "entity2": "C", "span1": [42, 47], "span2": [160, 161]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10549": {"label": 2, "data": {"text": "A novel retinoic acid-responsive element regulates retinoic acid-induced BLR1 expression.", "entity1": "BLR1", "entity2": "retinoic acid", "span1": [73, 77], "span2": [51, 64]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8871": {"label": 3, "data": {"text": "Phosphorylation of c-Src, which was shown to be activated by AhR ligands, was also increased by I3S and TCDD, and blocking of c-Src activity by 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine (PP2) inhibited phosphorylation of both c-Src and STAT3, raising a possibility that stimulatory activities of I3S and TCDD on Th17 differentiation could be exerted via increased phosphorylation of c-Src, which in turn stimulates STAT3 activation.", "entity1": "c-Src", "entity2": "4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine", "span1": [249, 254], "span2": [144, 208]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14352": {"label": 3, "data": {"text": "mRNA levels of receptor activator of nuclear factor kappa-B (RANK), its ligand RANKL, tumor necrosis factor alpha (TNF-\u03b1) and RANKL/osteoprotegerin (OPG) ratio were diminished in the periodontium of CCL3(-/-) mice and in the group treated with Met-RANTES.", "entity1": "TNF-\u03b1", "entity2": "Met", "span1": [115, 120], "span2": [244, 247]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5596": {"label": 1, "data": {"text": "The patients were divided into two groups according to the 5HT-2A affinity of the individual medications (high 5HT-2A affinity--clozapine, olanzapine, risperidone vs. low 5HT-2A affinity--quetiapine, amisulpride).", "entity1": "5HT-2A", "entity2": "amisulpride", "span1": [171, 177], "span2": [200, 211]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13825": {"label": 3, "data": {"text": "CYP2D6 inhibitors, such as paroxetine, are associated with changes in atomoxetine pharmacokinetics similar to those observed among poor CYP2D6 metabolizers.", "entity1": "CYP2D6", "entity2": "paroxetine", "span1": [0, 6], "span2": [27, 37]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10406": {"label": 1, "data": {"text": "Unlike OFQ II(1-17), high concentrations of its C-terminal extension, OFQ II(1-28), stimulated [35S]-GTPgammaS binding in a mu (mu) opioid receptor-like distribution and the effect was blocked by naloxone.", "entity1": "OFQ II(1-17)", "entity2": "[35S]-GTPgammaS", "span1": [7, 19], "span2": [95, 110]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13423": {"label": 9, "data": {"text": "TGF-beta1 and high D-glucose increased hCAT-1 mRNA expression ( approximately 8-fold) and maximal transport velocity (V(max)), L-[(3)H]citrulline formation from L-[(3)H]arginine (index of NO synthesis) and endothelial NO synthase (eNOS) protein abundance, but did not alter eNOS phosphorylation.", "entity1": "eNOS", "entity2": "L-[(3)H]citrulline", "span1": [274, 278], "span2": [127, 145]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, 9]},
	"9140": {"label": 1, "data": {"text": "Certain analogs of caffeine in which the methyl group at the 1- or 7-position is replaced with a propargyl or propyl group display selectivity for A2 receptors.", "entity1": "A2 receptors", "entity2": "methyl", "span1": [147, 159], "span2": [41, 47]}, "weak_labels": [-1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7167": {"label": 4, "data": {"text": "OBJECTIVE: Telmisartan, an angiotensin II type 1 receptor (AT1R) antagonist, was found to have a unique property: it is a partial agonist of peroxisome proliferator-activated receptor gamma (PPARgamma).", "entity1": "peroxisome proliferator-activated receptor gamma", "entity2": "Telmisartan", "span1": [141, 189], "span2": [11, 22]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4264": {"label": 1, "data": {"text": "Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, GSK3\u03b2 phosphorylation, cleaved PARP and deceased AEG-1 induced by ursolic acid in HepG2 cells.", "entity1": "PARP", "entity2": "ursolic acid", "span1": [100, 104], "span2": [135, 147]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10252": {"label": 2, "data": {"text": "In no other subject any activation of platelets by GP IIb/IIIa inhibitors was observed and there were no statistically significant differences between HPA-1 genotypes with respect to the effects of GP IIb/IIIa inhibitors on basal or ADP-stimulated CD62P expression.", "entity1": "CD62P", "entity2": "ADP", "span1": [248, 253], "span2": [233, 236]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9666": {"label": 1, "data": {"text": "Eosinophils were isolated from peripheral blood, treated with either buffer or 10(-)10 M to 10(-)6 M FP in the presence of 10 pg/ml human recombinant interleukin-5 (rhIL-5) and activated with formyl-met-leu-phe (FMLP) + cytochalasin B (CB).", "entity1": "rhIL-5", "entity2": "FMLP", "span1": [165, 171], "span2": [212, 216]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5414": {"label": 8, "data": {"text": "In functional transport assays, we found that one of the identified molecules, ATM7, increased the reuptake of serotonin, possibly by facilitating the interaction of serotonin with transport-ready conformations of SERT when concentrations of serotonin were low and rate limiting.", "entity1": "SERT", "entity2": "serotonin", "span1": [214, 218], "span2": [111, 120]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"2839": {"label": 2, "data": {"text": "The enzyme requires PLP and divalent cations such as Ca(2+), Mg(2+), or Mn(2+), but not ATP, whereas mammalian serine racemase activity is increased by ATP.", "entity1": "serine racemase", "entity2": "ATP", "span1": [111, 126], "span2": [152, 155]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"4014": {"label": 3, "data": {"text": "Compared with the untreated colitis group, the curcumin-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-\u03baB mRNA, IL-27 mRNA, TLR4 protein, NF-\u03baB p65 protein, and IL-27 p28 protein (p < 0.05).", "entity1": "p28", "entity2": "curcumin", "span1": [291, 294], "span2": [47, 55]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6458": {"label": 4, "data": {"text": "METHODS: Different classes of antidepressants [imipramine (tricyclic), maprotiline (noradrenline reuptake inhibitor), venlafaxine (mixed serotonin and noradrenaline reuptake inhibitors), fluvoxamine and sertraline (selective serotonin reuptake inhibitor)] were tested in the same randomised experimental session, alone and in combination with 5-HT1A and 5-HT1B receptor agonists [buspirone (partial 5-HT1A agonist), anpirtoline (5-HT1B agonist)] in the mouse forced swimming test.", "entity1": "5-HT1B", "entity2": "anpirtoline", "span1": [429, 435], "span2": [416, 427]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"413": {"label": 1, "data": {"text": "(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned human alpha 1D adrenoceptors.", "entity1": "human alpha 1D adrenoceptors", "entity2": "(-)-tamsulosin", "span1": [258, 286], "span2": [16, 30]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"359": {"label": 1, "data": {"text": "A cocaine-sensitive, high-affinity Drosophila serotonin (5-hydroxytryptamine; 5HT) transporter cDNA, denoted dSERT1, was isolated and characterized in oocytes.", "entity1": "dSERT1", "entity2": "cocaine", "span1": [109, 115], "span2": [2, 9]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, 9]},
	"5438": {"label": 3, "data": {"text": "A series of benzenesulfonamides incorporating cyanoacrylamide moieties (tyrphostine analogs) were assayed as inhibitors of the \u03b2-carbonic anhydrase (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA.", "entity1": "CA", "entity2": "cyanoacrylamide", "span1": [149, 151], "span2": [46, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11110": {"label": 1, "data": {"text": "Dopamine D2-receptor imaging with 123I-iodobenzamide SPECT in migraine patients abusing ergotamine: does ergotamine cross the blood brain barrier?", "entity1": "Dopamine D2-receptor", "entity2": "ergotamine", "span1": [0, 20], "span2": [88, 98]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10124": {"label": 5, "data": {"text": "A nicotinic receptor antagonist (hexamethonium) attenuated the contraction in part and an alpha-adrenoceptor antagonist (prazosin) nearly abolished the contraction.", "entity1": "alpha-adrenoceptor", "entity2": "prazosin", "span1": [90, 108], "span2": [121, 129]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7270": {"label": 3, "data": {"text": "Some clinically used compounds, such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, sulpiride, and indisulam, or the orphan drug benzolamide, showed effective hCA VI inhibitory activity, with inhibition constants of 0.8-79 nM.", "entity1": "hCA VI", "entity2": "topiramate", "span1": [218, 224], "span2": [131, 141]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12647": {"label": 1, "data": {"text": "Salicylic acid promotes dissociation of (125)I-ET-1 ETA receptor complexes both in the absence and the presence of unlabeled ET-1.", "entity1": "ET-1", "entity2": "(125)I", "span1": [47, 51], "span2": [40, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10676": {"label": 3, "data": {"text": "In conclusion, TT-235 may inhibit the uterine response to oxytocin by decreasing oxytocin receptor numbers and oxytocin binding affinity, which might explain the prolonged oxytocin antagonist activity of TT-235.", "entity1": "oxytocin", "entity2": "TT-235", "span1": [58, 66], "span2": [15, 21]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1483": {"label": 9, "data": {"text": "Similarly, pretreatment with sulindac sulfide blocks the ability of EGF to induce ERK1/2 and Bad phosphorylation, but also down-regulates total Bad but not ERK1/2 protein levels.", "entity1": "ERK1/2", "entity2": "sulindac sulfide", "span1": [82, 88], "span2": [29, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"2220": {"label": 4, "data": {"text": "Systemic administration of beta2-adrenoceptor agonists, formoterol and salmeterol, elicit skeletal muscle hypertrophy in rats at micromolar doses.", "entity1": "beta2-adrenoceptor", "entity2": "salmeterol", "span1": [27, 45], "span2": [71, 81]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3440": {"label": 1, "data": {"text": "LY541850 was claimed from human mGlu receptors expressed in non-neuronal cells to be a selective orthosteric mGlu2 agonist and mGlu3 antagonist.", "entity1": "human mGlu receptors", "entity2": "LY541850", "span1": [26, 46], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8823": {"label": 3, "data": {"text": "Exhibiting unique properties over other MMPIs (e.g., hydroxamates), these newly reported compounds are capable of modulating activities of several MMPs in the low nanomolar range, including MMP-2 (~2 to 50 nM), MMP-13 (~2 to 50 nM), and MMP-14 (~4 to 60 nM).", "entity1": "MMPs", "entity2": "hydroxamates", "span1": [147, 151], "span2": [53, 65]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1694": {"label": 5, "data": {"text": "Considerable attention has focused on the investigation of theories to explain the better tolerability of memantine over other NMDA receptor antagonists, particularly those that act by a similar channel blocking mechanism such as dissociative anesthetic-like agents (phencyclidine, ketamine, MK-801).", "entity1": "NMDA receptor", "entity2": "memantine", "span1": [127, 140], "span2": [106, 115]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10655": {"label": 3, "data": {"text": "Valdecoxib potently inhibits recombinant COX-2, with an IC(50) of 0.005 microM; this compares with IC values of 0.05 microM for celecoxib, 0.5 microM for rofecoxib, and 5 microM for etoricoxib.", "entity1": "COX-2", "entity2": "etoricoxib", "span1": [41, 46], "span2": [182, 192]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11768": {"label": 0, "data": {"text": "Incubation of purified Pin1 with HNE followed by MALDI-TOF/TOF mass spectrometry resulted in detection of Michael adducts at the active site residues His-157 and Cys-113.", "entity1": "Pin1", "entity2": "Cys", "span1": [23, 27], "span2": [162, 165]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13144": {"label": 1, "data": {"text": "Cysteinyl leukotriene receptor 1 is involved in N-methyl-D-aspartate-mediated neuronal injury in mice.", "entity1": "Cysteinyl leukotriene receptor 1", "entity2": "N-methyl-D-aspartate", "span1": [0, 32], "span2": [48, 68]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1605": {"label": 3, "data": {"text": "5-(N,N-dimethyl)-amiloride (50 microM; DMA), a concentration that selectively inhibits the NHE isoforms NHE1 and NHE2, but not NHE3, did not affect DBS.", "entity1": "NHE3", "entity2": "5-(N,N-dimethyl)-amiloride", "span1": [127, 131], "span2": [0, 26]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3453": {"label": 1, "data": {"text": "R-modafinil was significantly less potent in the DAT Y156F mutant compared with wild-type DAT, whereas S-modafinil was affected less.", "entity1": "DAT", "entity2": "R-modafinil", "span1": [90, 93], "span2": [0, 11]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2512": {"label": 3, "data": {"text": "IRF3 activation induced by MyD88-independent signaling components, TRIF and TBK1, was also downregulated by auranofin.", "entity1": "TBK1", "entity2": "auranofin", "span1": [76, 80], "span2": [108, 117]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7075": {"label": 1, "data": {"text": "Similar to menthol, both camphor and cinnamaldehyde (initially reported to be specific activators of TRPV3 and TRPA1, respectively) also modulate other thermoTRPs.", "entity1": "thermoTRPs", "entity2": "camphor", "span1": [152, 162], "span2": [25, 32]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15086": {"label": 1, "data": {"text": "Potential future roles for ceftazidime-avibactam include the treatment of suspected or documented infections caused by resistant Gram-negative-bacilli producing extended-spectrum \u00df-lactamase (ESBL), Klebsiella pneumoniae carbapenemases (KPCs) and/or AmpC \u00df-lactamases.", "entity1": "KPCs", "entity2": "avibactam", "span1": [237, 241], "span2": [39, 48]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"280": {"label": 2, "data": {"text": "Both BRL and SAL produced a significant increase in postural finger tremor in keeping with beta 2-adrenoceptor stimulation, and this response was totally abolished by pretreatment with N20.", "entity1": "beta 2-adrenoceptor", "entity2": "SAL", "span1": [91, 110], "span2": [13, 16]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"476": {"label": 5, "data": {"text": "The potency of the antipsychotic drug, risperidone, to antagonize alpha 1A-adrenoceptor-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and alpha 1B-adrenoceptor-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of alpha 1-adrenoceptor subtype-discriminating antagonists.", "entity1": "alpha 1B-adrenoceptor", "entity2": "risperidone", "span1": [178, 199], "span2": [39, 50]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12957": {"label": 9, "data": {"text": "Calcium-chelating reagents such as EDTA and 1,2-bis-(o-aminphenoxy)-ethane-N,N,N',N'-tetra-acetic acid tetra-acetoxy-methyl ester prevented the cleavage of GAD65.", "entity1": "GAD65", "entity2": "1,2-bis-(o-aminphenoxy)-ethane-N,N,N',N'-tetra-acetic acid tetra-acetoxy-methyl ester", "span1": [156, 161], "span2": [44, 129]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5835": {"label": 8, "data": {"text": "The unique role of the enzyme 5-lipoxygenase (5-LO) in the production of leukotrienes (LTs) makes it a likely target for biochemical manipulation.", "entity1": "5-LO", "entity2": "LTs", "span1": [46, 50], "span2": [87, 90]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"15678": {"label": 3, "data": {"text": "Moreover, curcumin could also down-regulate the expression and activity of matrix metalloproteinase-9 (MMP-9).", "entity1": "MMP-9", "entity2": "curcumin", "span1": [103, 108], "span2": [10, 18]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"718": {"label": 1, "data": {"text": "Tyrosine hydroxylase binds tetrahydrobiopterin cofactor with negative cooperativity, as shown by kinetic analyses and surface plasmon resonance detection.", "entity1": "Tyrosine hydroxylase", "entity2": "tetrahydrobiopterin", "span1": [0, 20], "span2": [27, 46]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 7, -1, -1, -1, -1, -1, -1]},
	"4976": {"label": 2, "data": {"text": "Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN.", "entity1": "caspase 3", "entity2": "Crocin", "span1": [181, 190], "span2": [0, 6]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13356": {"label": 2, "data": {"text": "INTRODUCTION: Medroxyprogesterone acetate (MPA) induces estrogen receptor (ER)-positive and progesterone receptor (PR)-positive ductal invasive mammary carcinomas in BALB/c mice.", "entity1": "ER", "entity2": "MPA", "span1": [75, 77], "span2": [43, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15193": {"label": 8, "data": {"text": "Upon studying the drug-drug interaction of darunavir with ketoconazole, data were indicative for an inhibitory effect of ketoconazole on P-gp as the main mechanism for the increased transport of darunavir across the small intestine.", "entity1": "P-gp", "entity2": "darunavir", "span1": [137, 141], "span2": [195, 204]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"13436": {"label": 2, "data": {"text": "Elevated extracellular D-glucose increases transforming growth factor beta1 (TGF-beta1) release from human umbilical vein endothelium (HUVEC).", "entity1": "TGF-beta1", "entity2": "D-glucose", "span1": [77, 86], "span2": [23, 32]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2066": {"label": 3, "data": {"text": "We previously reported that aminoglycoside antibiotics reduce SGLT1-dependent glucose transport in pig proximal tubular epithelial LLC-PK1 cells in parallel with the order of their nephrotoxicity.", "entity1": "SGLT1", "entity2": "aminoglycoside", "span1": [62, 67], "span2": [28, 42]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"4790": {"label": 8, "data": {"text": "Concentration-dependent inhibitory effects of baicalin on the metabolism of dextromethorphan, a dual probe of CYP2D and CYP3A, in rats.", "entity1": "CYP2D", "entity2": "dextromethorphan", "span1": [110, 115], "span2": [76, 92]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15781": {"label": 3, "data": {"text": "Aminopropylindenes derived from Grundmann's ketone as a novel chemotype of oxidosqualene cyclase inhibitors.", "entity1": "oxidosqualene cyclase", "entity2": "Grundmann's ketone", "span1": [75, 96], "span2": [32, 50]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"558": {"label": 5, "data": {"text": "Both the 5 alpha-reductase inhibitor finasteride and alpha 1-adrenoceptor antagonists (e.g. alfuzosin, doxazosin, prazosin, tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials.", "entity1": "alpha 1-adrenoceptor", "entity2": "prazosin", "span1": [53, 73], "span2": [114, 122]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3074": {"label": 3, "data": {"text": "PURPOSE: To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).", "entity1": "GABA transaminase", "entity2": "VIG", "span1": [311, 328], "span2": [244, 247]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13532": {"label": 7, "data": {"text": "Mammalian cysteine dioxygenase (CDO) is a non-heme iron metalloenzyme that catalyzes the first committed step in oxidative cysteine catabolism.", "entity1": "Mammalian cysteine dioxygenase", "entity2": "iron", "span1": [0, 30], "span2": [51, 55]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"8756": {"label": 8, "data": {"text": "Kinetic analyses revealed that the affinity and clearance of UGT2B10 for amitriptyline, imipramine, and diphenhydramine are significantly higher than the corresponding values of UGT1A4 and UGT1A3, although the Vmax values of UGT1A4 toward these drugs are considerably higher.", "entity1": "UGT1A4", "entity2": "imipramine", "span1": [225, 231], "span2": [88, 98]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10689": {"label": 3, "data": {"text": "However, consistent with its low COX-1 inhibitory activity, lumiracoxib at a dose of 100 mg kg(-1) orally caused no ulcers and was significantly less ulcerogenic than diclofenac (P<0.05).", "entity1": "COX-1", "entity2": "lumiracoxib", "span1": [33, 38], "span2": [60, 71]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14454": {"label": 2, "data": {"text": "We observed similar effects of Ag NPs on inflammatory mediator expression in vitro and in vivo with increase of interleukin-8 (IL-8)/macrophage inflammatory protein 2, IL-1RI, and tumor necrosis factor-\u03b1 expression in both models and increased IL-8 protein release in vitro.", "entity1": "tumor necrosis factor-\u03b1", "entity2": "Ag", "span1": [180, 203], "span2": [31, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10398": {"label": 9, "data": {"text": "Taken together, these findings support the view that (1) OFQ is the only ppOFQ peptide that binds to and activates the ORL1 receptor and (2) OFQ II(1-28) does not bind or stimulate [35S]-GTPgammaS binding in cells expressing the mu opioid receptor.", "entity1": "mu opioid receptor", "entity2": "[35S]-GTPgammaS", "span1": [229, 247], "span2": [181, 196]}, "weak_labels": [-1, -1, -1, 1, -1, -1, 2, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9660": {"label": 1, "data": {"text": "FMLP/CB-stimulated translocation of cPLA2 to the nuclear envelope assessed by specific immunohistochemical staining also was blocked by FP.", "entity1": "cPLA2", "entity2": "CB", "span1": [36, 41], "span2": [5, 7]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14438": {"label": 2, "data": {"text": "Induction of AhR by TCDD and prochloraz resulted in a time- and dose-dependent increase of ABCG2 gene expression and transporter protein levels.", "entity1": "ABCG2", "entity2": "TCDD", "span1": [91, 96], "span2": [20, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"15930": {"label": 1, "data": {"text": "Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is well studied in the nervous system and described as a dynamic modulator of plastic processes like precursor cell migration, axon fasciculation, and synaptic plasticity.", "entity1": "NCAM", "entity2": "polySia", "span1": [69, 73], "span2": [95, 102]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"847": {"label": 3, "data": {"text": "OBJECTIVE: This randomized, double-blind study tested the hypothesis that rofecoxib, a drug that specifically inhibits cyclooxygenase 2, would cause fewer gastroduodenal ulcers than ibuprofen (in a multicenter trial), and its side effects would be equivalent to those of placebo (in a prespecified analysis combining the results with another trial of identical design).", "entity1": "cyclooxygenase 2", "entity2": "rofecoxib", "span1": [119, 135], "span2": [74, 83]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"14044": {"label": 9, "data": {"text": "mTOR was still inhibited by aspirin in CRC cells after siRNA knockdown of AMPKalpha, indicating AMPK-dependent and AMPK-independent mechanisms of aspirin-induced inhibition of mTOR.", "entity1": "AMPK", "entity2": "aspirin", "span1": [115, 119], "span2": [146, 153]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15269": {"label": 0, "data": {"text": "We report for the first time that VEGF-D binds heparin, and that the C-terminal propeptide significantly enhances this interaction (removal of this propeptide from full-length VEGF-D completely prevents heparin binding).", "entity1": "VEGF-D", "entity2": "C", "span1": [176, 182], "span2": [69, 70]}, "weak_labels": [-1, -1, -1, 1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15818": {"label": 0, "data": {"text": "In the present report, we show that Fer associates with the activated PDGFbeta receptor (PDGFRbeta) through multiple autophosphorylation sites, i.e. Tyr579, Tyr581, Tyr740 and Tyr1021.", "entity1": "PDGFRbeta", "entity2": "Tyr", "span1": [89, 98], "span2": [165, 168]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14234": {"label": 1, "data": {"text": "A combination of nerve agent therapy drugs (oxime, anti-muscarinic, anticonvulsant) with huBuChE (i.m.)", "entity1": "huBuChE", "entity2": "oxime", "span1": [89, 96], "span2": [44, 49]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14364": {"label": 3, "data": {"text": "The quinolizidine alkaloids (natural products) such as oxymatrine, sophoridine, sophocarpine and matrine carry the common molecular structure of O=C=N-C-C-C-N that possessed positive ionotropic effect and hERG blocking activity.", "entity1": "hERG", "entity2": "oxymatrine", "span1": [205, 209], "span2": [55, 65]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 9]},
	"14427": {"label": 3, "data": {"text": "Metformin directly inhibits ghrelin secretion through AMP-activated protein kinase in rat primary gastric cells.", "entity1": "ghrelin", "entity2": "Metformin", "span1": [28, 35], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14290": {"label": 9, "data": {"text": "Valpromide (VPD), the amide derivative of VPA, does not inhibit HDAC activity and is a weak teratogen in vivo.", "entity1": "HDAC", "entity2": "VPA", "span1": [64, 68], "span2": [42, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"12826": {"label": 8, "data": {"text": "In the present study, age-related changes of pyridoxal 5'-phosphate (PLP) synthesizing enzymes, pyridoxal kinase (PLK) and pyridoxine 5'-phosphate oxidase (PNPO), their protein contents and activities were examined in the gerbil hippocampus proper.", "entity1": "pyridoxal kinase", "entity2": "pyridoxal 5'-phosphate", "span1": [96, 112], "span2": [45, 67]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15836": {"label": 1, "data": {"text": "The expression of ABCA1 and ABCG1 was induced by 24-OHC, as well as TO901317 and retinoic acid, which are ligands of the nuclear receptors LXR/RXR.", "entity1": "nuclear receptors", "entity2": "TO901317", "span1": [121, 138], "span2": [68, 76]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14264": {"label": 8, "data": {"text": "By contrast, 1,12-diamino-3,6,9-triazadodecane(SpmTrien), a charge-deficient spermine analog, was an extremely poor substrate of human recombinant SSAT2 and was metabolized by SSAT1 in HEPG2 cells and in wild-type primary hepatocytes.", "entity1": "human recombinant SSAT2", "entity2": "spermine", "span1": [129, 152], "span2": [77, 85]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"14790": {"label": 2, "data": {"text": "Human immortalized corneal fibroblasts were treated with TGF-\u03b2 in the presence of TSA, the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI), the antioxidant N-acetyl-cysteine (NAC), the NF-E2-related factor 2-antioxidant response element (Nrf2-ARE) activator sulforaphane, or small interfering RNA.", "entity1": "antioxidant response element", "entity2": "sulforaphane", "span1": [212, 240], "span2": [262, 274]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3957": {"label": 1, "data": {"text": "Moreover, VK2-2,3 epoxide, an intracellular metabolite of VK2, was shown to covalently bind to the cysteine-166 residue of Bak.", "entity1": "Bak", "entity2": "VK2-2,3 epoxide", "span1": [123, 126], "span2": [10, 25]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6333": {"label": 1, "data": {"text": "Among the current AT1 receptor antagonists, the rank order of the relative binding affinities (highest affinity = 1) is: candesartan 1, telmisartan 10, E3174 (the active metabolite of losartan) 10, tasosartan 20, losartan 50, eprosartan 100 and the prodrug candesartan cilexetil 280.", "entity1": "AT1", "entity2": "candesartan", "span1": [18, 21], "span2": [121, 132]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9632": {"label": 1, "data": {"text": "Analogous to the antiandrogens, bicalutamide and hydroxyflutamide, binding of estramustine phosphate metabolites to the androgen receptor was observed.", "entity1": "androgen receptor", "entity2": "hydroxyflutamide", "span1": [120, 137], "span2": [49, 65]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5385": {"label": 1, "data": {"text": "Further, methylphenidate did not alter DAT cellular localization, indicating that methylphenidate treatment during adolescence regulated DAT function in SHR mPFC in a trafficking-independent manner.", "entity1": "DAT", "entity2": "methylphenidate", "span1": [137, 140], "span2": [82, 97]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"14660": {"label": 0, "data": {"text": "Genistein also reduced the formation of stress fibers by thrombin and suppressed thrombin-induced phosphorylation of myosin light chain (MLC) on Ser(19)/Thr(18) in endothelial cells (ECs).", "entity1": "MLC", "entity2": "Ser", "span1": [137, 140], "span2": [145, 148]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1397": {"label": 3, "data": {"text": "Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astrocytes.", "entity1": "cytokine", "entity2": "Gemfibrozil", "span1": [46, 54], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"8793": {"label": 3, "data": {"text": "Treatment with CAPE decreased protein abundance of Akt, Akt1, Akt2, Akt3, phospho-Akt Ser473, phospho-Akt Thr 308, GSK3\u03b2, FOXO1, FOXO3a, phospho-FOXO1 Thr24, phospho-FoxO3a Thr32, NF-\u03baB, phospho-NF-\u03baB Ser536, Rb, phospho-Rb Ser807/811, Skp2, and cyclin D1, but increased cell cycle inhibitor p27Kip.", "entity1": "Skp2", "entity2": "CAPE", "span1": [236, 240], "span2": [15, 19]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5006": {"label": 1, "data": {"text": "This study is the first to identify Class V CGPs with their distinctive methine or trimethine linkage between two disubstituted pyrylium moieties as a particularly potent class of MRP modulators and also show that within this core structure, differences in the electronegativity associated with a chalcogen atom can be the sole determinant of whether a compound will stimulate or inhibit MRP2.", "entity1": "MRP", "entity2": "trimethine", "span1": [180, 183], "span2": [83, 93]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6449": {"label": 3, "data": {"text": "The present studies were undertaken to compare two compounds, a vitamin D(3) analogue (CB1093) with minimal calcaemic effects, and clenbuterol, a long-acting beta(2)-adrenoceptor agonist, both of which induce NGF synthesis in vivo.", "entity1": "NGF", "entity2": "vitamin D(3)", "span1": [209, 212], "span2": [64, 76]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1482": {"label": 8, "data": {"text": "Racemization of serine is catalyzed by serine racemase, a pyridoxal 5'-phosphate-dependent enzyme expressed mainly in brain and liver.", "entity1": "serine racemase", "entity2": "serine", "span1": [39, 54], "span2": [16, 22]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"15905": {"label": 1, "data": {"text": "Synaptotagmin 1 is required for vesicular Ca(2+) /H(+) -antiport activity.", "entity1": "Synaptotagmin 1", "entity2": "H(+)", "span1": [0, 15], "span2": [50, 54]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2201": {"label": 3, "data": {"text": "We also assessed the potential relevant signaling pathway in vitro to elucidate the mechanisms underlying the MMP-9 inhibition by tetracyclines.", "entity1": "MMP-9", "entity2": "tetracyclines", "span1": [110, 115], "span2": [130, 143]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6923": {"label": 1, "data": {"text": "Furthermore, HM74A, but not HM74, expressed in differentiated 3T3L1 adipocytes effectively mediated inhibition of lipolysis by niacin.", "entity1": "HM74A", "entity2": "niacin", "span1": [13, 18], "span2": [127, 133]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1201": {"label": 3, "data": {"text": "We evaluated the effect of anastrozole, a more selective aromatase inhibitor, on the hormonal and semen profiles of infertile men with abnormal baseline testosterone-to-estradiol ratios.", "entity1": "aromatase", "entity2": "anastrozole", "span1": [57, 66], "span2": [27, 38]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15288": {"label": 3, "data": {"text": "Mice given daily injections of high dose JZL184 (\u226516 mg/kg) for six days displayed decreased CB(1) receptor density and function in brain, as assessed in [(3)H]SR141716A binding and CP55,940-stimulated [(35)S]GTP\u03b3S binding assays, respectively.", "entity1": "CB(1)", "entity2": "JZL184", "span1": [93, 98], "span2": [41, 47]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15797": {"label": 8, "data": {"text": "The ATP required for potentiation of skeletal muscle contraction is released via pannexin hemichannels.", "entity1": "pannexin", "entity2": "ATP", "span1": [81, 89], "span2": [4, 7]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6881": {"label": 8, "data": {"text": "Cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS) utilize L-cysteine as substrate to form H2S.", "entity1": "cystathionine-beta-synthase", "entity2": "L-cysteine", "span1": [36, 63], "span2": [78, 88]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"11431": {"label": 1, "data": {"text": "In the presence of alphaAR blockade, concentration-response curves for isoproterenol, norepinephrine, and epinephrine suggested that a beta1AR was involved in this response, and the rank order of potency was isoproterenol > norepinephrine = epinephrine.", "entity1": "beta1AR", "entity2": "isoproterenol", "span1": [135, 142], "span2": [208, 221]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7269": {"label": 3, "data": {"text": "Some clinically used compounds, such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, sulpiride, and indisulam, or the orphan drug benzolamide, showed effective hCA VI inhibitory activity, with inhibition constants of 0.8-79 nM.", "entity1": "hCA VI", "entity2": "brinzolamide", "span1": [218, 224], "span2": [117, 129]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9308": {"label": 2, "data": {"text": "Histamine enhances the depolarizing afterpotential of immunohistochemically identified vasopressin neurons in the rat supraoptic nucleus via H1-receptor activation.", "entity1": "H1-receptor", "entity2": "Histamine", "span1": [141, 152], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14606": {"label": 8, "data": {"text": "Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.", "entity1": "Ala119Gly", "entity2": "Ara-C", "span1": [81, 90], "span2": [222, 227]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"3975": {"label": 8, "data": {"text": "These results suggest that CYP2B6 genotype is the most important patient variable for predicting the level of CYP2B6 activity in women, when measured by the metabolism of bupropion.", "entity1": "CYP2B6", "entity2": "bupropion", "span1": [110, 116], "span2": [171, 180]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"5789": {"label": 9, "data": {"text": "A cDNA encoding the complete amino acid sequence of aminoacylase 1 (N-acylamino acid aminohydrolase, ACY-1) [EC 3.5.1.14], a dimeric metalloprotein having two Zn2+ in the molecule, which catalyzes the deacylation of N-acylated L-amino acids except L-aspartic acid, has been isolated from porcine kidney lambda gt10 cDNA library and sequenced.", "entity1": "N-acylamino acid aminohydrolase", "entity2": "L-aspartic acid", "span1": [68, 99], "span2": [248, 263]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"12201": {"label": 3, "data": {"text": "A significant positive correlation was found between dietary intake of total SFAs and total MUFAs and expression of PBMC D6D and D5D genes, but a significant negative correlation between dietary intake of linoleic acid (LA) and alpha-linolenic acid (LNA) and the expression of PBMC D6D and D5D genes.", "entity1": "D5D", "entity2": "LA", "span1": [290, 293], "span2": [220, 222]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15848": {"label": 2, "data": {"text": "The expression of ABCA1 and ABCG1 was induced by 24-OHC, as well as TO901317 and retinoic acid, which are ligands of the nuclear receptors LXR/RXR.", "entity1": "ABCA1", "entity2": "TO901317", "span1": [18, 23], "span2": [68, 76]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3840": {"label": 1, "data": {"text": "Linking GABA(A) receptor subunits to alcohol-induced conditioned taste aversion and recovery from acute alcohol intoxication.", "entity1": "GABA(A) receptor", "entity2": "alcohol", "span1": [8, 24], "span2": [37, 44]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7037": {"label": 8, "data": {"text": "The tissue RA level is maintained through a cascade of metabolic reactions where retinal dehydrogenases (RALDHs) catalyze the terminal reaction of RA biosynthesis from retinal, a rate-limiting step.", "entity1": "RALDHs", "entity2": "RA", "span1": [105, 111], "span2": [147, 149]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"5405": {"label": 1, "data": {"text": "Results demonstrate that LRRK2 down-regulation potentiates Mn toxicity in both control and DAT-transfected cell as well as potentiates DA toxicity.", "entity1": "DAT", "entity2": "Mn", "span1": [91, 94], "span2": [59, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15648": {"label": 1, "data": {"text": "In contrast, the latter pathway likely involves MHC binding peptides displayed as a consequence of abacavir exposure, but not abacavir itself.", "entity1": "MHC", "entity2": "abacavir", "span1": [48, 51], "span2": [99, 107]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"4534": {"label": 3, "data": {"text": "Given these findings, a unified PK model including the inhibition of MAO-A- and CYP2D6-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.", "entity1": "CYP2D6", "entity2": "harmaline", "span1": [237, 243], "span2": [163, 172]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"6006": {"label": 0, "data": {"text": "The protein that binds TSG-6 was purified from human serum and identified as inter-alpha-inhibitor (I alpha I) by N-terminal microsequencing.", "entity1": "I alpha I", "entity2": "N", "span1": [100, 109], "span2": [114, 115]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10383": {"label": 3, "data": {"text": "Investigation of bradykinin metabolism in human and rat plasma in the presence of the dual ACE/NEP inhibitors GW660511X and omapatrilat.", "entity1": "NEP", "entity2": "GW660511X", "span1": [95, 98], "span2": [110, 119]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14975": {"label": 1, "data": {"text": "RESULTS: In contrast to immune stimulatory sequence ISS 1018, BCG DNA spontaneously formed nanoparticulate structures and induced actin polymerization as did synthetic silica nanoparticles.", "entity1": "actin", "entity2": "silica", "span1": [130, 135], "span2": [168, 174]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5484": {"label": 1, "data": {"text": "At 37 degrees C the relative affinity of 3-keto-desogestrel for the androgen receptor in intact MCF-7 cells was half that of levonorgestrel, similar to that of norethisterone and medroxyprogesterone acetate (MPA) and at least three times higher than that of progestagens with anti-androgenic activity whereas at 4 degrees C in the cytosol fraction exposed to molybdate there was no clear difference between the relative affinities of progestagens with androgenic and anti-androgenic properties.", "entity1": "androgen receptor", "entity2": "medroxyprogesterone acetate", "span1": [68, 85], "span2": [179, 206]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14486": {"label": 8, "data": {"text": "Of the rat CYP isoforms studied, CYP2D isoforms were the most efficient in catalyzing the O-demethylation of 5-methoxytryptamine to serotonin, but they were less effective than the human isoform CYP2D6.", "entity1": "human isoform CYP2D6", "entity2": "O", "span1": [181, 201], "span2": [90, 91]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"1585": {"label": 3, "data": {"text": "The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "entity1": "acetylcholinesterase", "entity2": "4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine", "span1": [4, 24], "span2": [231, 306]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8417": {"label": 3, "data": {"text": "Moreover, since reduced levels of p21CIP1 and Chk2 proteins but no change in p53 levels could be detected in MCF-7 cells after BSC 3g or 3n treatment our results suggest that BSC treated cells die from lethal mitosis.", "entity1": "p21CIP1", "entity2": "BSC", "span1": [34, 41], "span2": [127, 130]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10344": {"label": 2, "data": {"text": "Arsenite triggered strong induction of HSPs, which was prevented by 1 micro g/mL cycloheximide (CXH).", "entity1": "HSPs", "entity2": "Arsenite", "span1": [39, 43], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10360": {"label": 2, "data": {"text": "GW660511X and omapatrilat increased the production of both BrBK1-8 and Br-Phe5 but not that of BrBK4-8 and BrBK2-8.", "entity1": "Br-Phe5", "entity2": "GW660511X", "span1": [71, 78], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 9]},
	"14103": {"label": 1, "data": {"text": "CRBN mediated antiproliferative activities of lenalidomide and pomalidomide in myeloma cells, as well as lenalidomide- and pomalidomide-induced cytokine production in T cells.", "entity1": "CRBN", "entity2": "pomalidomide", "span1": [0, 4], "span2": [63, 75]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"13149": {"label": 3, "data": {"text": "Pranlukast, ketamine and edaravone decreased NMDA-induced injury; pranlukast (0.1 mg/kg) and ketamine inhibited the upregulated expression of the CysLT1 receptor.", "entity1": "CysLT1 receptor", "entity2": "ketamine", "span1": [146, 161], "span2": [93, 101]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4583": {"label": 0, "data": {"text": "The approach is demonstrated by selective labeling of proteins in bacterial cells immobilized in the center of a laminar-flow microfluidic channel, where they are exposed to overlapping, opposed gradients of inducers of the N- and C-terminal MetRS fragments.", "entity1": "MetRS", "entity2": "N", "span1": [242, 247], "span2": [224, 225]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14469": {"label": 1, "data": {"text": "Seven point mutations were introduced into the conserved motif in the second extracellular loop (ECII) of EP3, resulting in acquisition of GTP-sensitive agonist binding.", "entity1": "EP3", "entity2": "GTP", "span1": [106, 109], "span2": [139, 142]}, "weak_labels": [-1, -1, 0, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6693": {"label": 2, "data": {"text": "TRPM8 (CMR1) is a Ca(2+)-permeable channel, which can be activated by low temperatures, menthol, eucalyptol and icilin.", "entity1": "Ca(2+)-permeable channel", "entity2": "icilin", "span1": [18, 42], "span2": [112, 118]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12974": {"label": 1, "data": {"text": "gammaPKC directly associated with DGKgamma through its accessory domain (AD), depending on Ca2+ as well as phosphatidylserine/diolein in vitro.", "entity1": "DGKgamma", "entity2": "diolein", "span1": [34, 42], "span2": [126, 133]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"605": {"label": 3, "data": {"text": "15d-PGJ2 did not block nuclear translocation or DNA-binding activity of the transcription factor NFkappaB, but it did inhibit the activity of an NFkappaB reporter construct, suggesting that the mechanism of suppression of microglial iNOS by 15d-PGJ2 may involve interference with NFkappaB transcriptional activity in the nucleus.", "entity1": "NFkappaB", "entity2": "15d-PGJ2", "span1": [145, 153], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7542": {"label": 3, "data": {"text": "To determine whether a metabolite formed by the action of MAO on PLZ may be responsible for the elevation in brain ORN observed, animals were pretreated with vehicle or the MAO inhibitor tranylcypromine (TCP) before vehicle or PLZ (15 mg/kg), and brains collected 3 h later.", "entity1": "MAO", "entity2": "tranylcypromine", "span1": [173, 176], "span2": [187, 202]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7931": {"label": 2, "data": {"text": "Glucosamine at 50\u00a0mM was demonstrated to elevate both the mRNA and protein expression of p53 and heme oxygenase-1 (HO-1), but also caused a reduction in p21 protein expression.", "entity1": "p53", "entity2": "Glucosamine", "span1": [89, 92], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10633": {"label": 1, "data": {"text": "Bosentan also decreased viability as measured by the LDH, MTT and propidium iodide assays, with a LOAEL approximately 200 microM; however, a significant decrease in viability was not observed with the alamar blue assay.", "entity1": "LDH", "entity2": "Bosentan", "span1": [53, 56], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3544": {"label": 2, "data": {"text": "Leukotriene D4 induces cognitive impairment through enhancement of CysLT\u2081 R-mediated amyloid-\u03b2 generation in mice.", "entity1": "amyloid-\u03b2", "entity2": "Leukotriene D4", "span1": [85, 94], "span2": [0, 14]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15546": {"label": 2, "data": {"text": "Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited DMN-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-\u03b1 (TNF-\u03b1) mRNA, and collagen type I and \u03b1-smooth muscle actin protein.", "entity1": "\u03b1-smooth muscle actin", "entity2": "DMN", "span1": [289, 310], "span2": [110, 113]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13347": {"label": 8, "data": {"text": "Lymphocytes possess the essential components of a cholinergic system, including acetylcholine (ACh); choline acetyltransferase (ChAT), its synthesizing enzyme; and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively).", "entity1": "ChAT", "entity2": "acetylcholine", "span1": [128, 132], "span2": [80, 93]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14415": {"label": 5, "data": {"text": "Herein, we report the identification and characterization of 3-(5-tert-butyl-isoxazol-3-yl)-2-[(3-chloro-phenyl)-hydrazono]-3-oxo-propionitrile (ESI-09), a novel noncyclic nucleotide EPAC antagonist that is capable of specifically blocking intracellular EPAC-mediated Rap1 activation and Akt phosphorylation, as well as EPAC-mediated insulin secretion in pancreatic \u03b2 cells.", "entity1": "EPAC", "entity2": "ESI-09", "span1": [183, 187], "span2": [145, 151]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"814": {"label": 1, "data": {"text": "SC-51089 (10(-5) M), a selective EP1-receptor antagonist, showed no effect on the PGE1- or PGE2-induced inhibition of the HVA ICa, thereby indicating that PGE1- and PGE2-induced inhibition of the HVA Ca2+ channels is possibly mediated by the EP3 receptor.", "entity1": "EP3 receptor", "entity2": "PGE1", "span1": [242, 254], "span2": [155, 159]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6463": {"label": 3, "data": {"text": "Pemetrexed disodium (Alimta, LY231514) is a novel, multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase.", "entity1": "glycinamide ribonucleotide formyl transferase", "entity2": "Alimta", "span1": [141, 186], "span2": [21, 27]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9059": {"label": 1, "data": {"text": "7-Hydroxy levomepromazine, 3-hydroxy levomepromazine and 7-hydroxy fluphenazine had only 10% of the potency of the parent drug in histamine H1 receptor binding, while the 7-hydroxy-metabolites of chlorpromazine and perphenazine had about 75% of the potency of the parent drug in this binding system.", "entity1": "histamine H1 receptor", "entity2": "7-hydroxy fluphenazine", "span1": [130, 151], "span2": [57, 79]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2035": {"label": 8, "data": {"text": "L-serine dehydratase (SDH), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield pyruvate or 2-oxobutyrate.", "entity1": "L-serine dehydratase", "entity2": "pyruvate", "span1": [0, 20], "span2": [167, 175]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"3146": {"label": 1, "data": {"text": "Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity.", "entity1": "TrkB", "entity2": "Amitriptyline", "span1": [69, 73], "span2": [0, 13]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2859": {"label": 8, "data": {"text": "4-Hydroxynonenal (4-HNE) is a mutagenic alpha,beta-unsaturated aldehyde produced during oxidative injury that is conjugated by several glutathione S-transferase (GST) isoforms.", "entity1": "glutathione S-transferase", "entity2": "4-HNE", "span1": [135, 160], "span2": [18, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"9724": {"label": 0, "data": {"text": "Amino acids between Ile(183) and Val(191) are necessary for proper factor IX activation, but additional sequence between Ser(195) and Ile(197) or between Phe(260) and Ser(265) is required for complete restoration of activation.", "entity1": "factor IX", "entity2": "Amino acids", "span1": [67, 76], "span2": [0, 11]}, "weak_labels": [0, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7521": {"label": 2, "data": {"text": "Compared with normal control group, PTZ-kindled mice had significantly higher levels of malondialdehyde, nitrite, myeloperoxidase but had lower levels of reduced glutathione in the whole brain homogenate.", "entity1": "myeloperoxidase", "entity2": "PTZ", "span1": [114, 129], "span2": [36, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8544": {"label": 3, "data": {"text": "Administration of bicuculline, a GABAA inhibitor, isolated a single response to \u03c9-agatoxin, which was characterized by a reduction in network activity.", "entity1": "\u03c9-agatoxin", "entity2": "bicuculline", "span1": [80, 90], "span2": [18, 29]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1093": {"label": 3, "data": {"text": "The capacity of acetylcholinesterase inhibitors, with the exception of tacrine and ambenonium, to displace bound [3H]-oxotremorine-M in preference to [3H]quinuclinidyl benzilate predicts that the former compounds could act as potential agonists at muscarinic receptors.", "entity1": "acetylcholinesterase", "entity2": "ambenonium", "span1": [16, 36], "span2": [83, 93]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9210": {"label": 1, "data": {"text": "We have found that certain naphthalenesulfonamides [e.g., N-6(-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7)] and phenothiazines [e.g., trifluoperazine (TFP)] induce a loss of cell-surface receptors for alpha 2-macroglobulin, and epidermal growth factor (EGF) in fibroblasts.", "entity1": "epidermal growth factor", "entity2": "phenothiazines", "span1": [236, 259], "span2": [120, 134]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"13653": {"label": 0, "data": {"text": "The distances between the protons H20 and H2, H18 and H2, and H18 and H4 are shorter following their binding to the PGIS in solution-down to within 5 A.", "entity1": "PGIS", "entity2": "H18", "span1": [116, 120], "span2": [46, 49]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11870": {"label": 1, "data": {"text": "We examined the effects of anthocyanidins (cyanidin, delphinidin, malvidin, peonidin, petunidin, pelargonidin) on the aryl hydrocarbon receptor (AhR)-CYP1A1 signaling pathway in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cells.", "entity1": "AhR", "entity2": "peonidin", "span1": [145, 148], "span2": [76, 84]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5104": {"label": 2, "data": {"text": "In addition, cobalt protoporphyrin (CoPP), a specific HO-1 inducer, predominantly suppressed LPS-induced NO production.", "entity1": "HO-1", "entity2": "CoPP", "span1": [54, 58], "span2": [36, 40]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"7535": {"label": 8, "data": {"text": "10), is an 18-kDa integral nuclear membrane protein that belongs to a superfamily of membrane-associated proteins in eicosanoid and glutathione metabolism that includes 5-lipoxygenase-activating protein, microsomal glutathione S-transferases (MGSTs), and microsomal prostaglandin E synthase 1 (ref.", "entity1": "microsomal glutathione S-transferases", "entity2": "glutathione", "span1": [204, 241], "span2": [132, 143]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6433": {"label": 3, "data": {"text": "However, AChE activity in triceps muscle decreased significantly (78% of control) in the group treated with pyridostigmine plus exercise.", "entity1": "AChE", "entity2": "pyridostigmine", "span1": [9, 13], "span2": [108, 122]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12478": {"label": 8, "data": {"text": "Cynomolgus FMO1, FMO2, FMO3, and FMO5 metabolized benzydamine, and FMO1/FMO3 and FMO3 also metabolized methimazole and trimethylamine, respectively.", "entity1": "Cynomolgus FMO1", "entity2": "benzydamine", "span1": [0, 15], "span2": [50, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7737": {"label": 3, "data": {"text": "Fulvestrant, a pure estrogen receptor downregulator, is a new addition to the antiestrogen therapeutic armamentarium since its FDA approval in 2002.", "entity1": "estrogen receptor", "entity2": "Fulvestrant", "span1": [20, 37], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11901": {"label": 3, "data": {"text": "Western blotting demonstrated that DMBT effectively suppressed the expression of VEGF, p-VEGFR-2, p-EGFR, and p-Akt.", "entity1": "VEGF", "entity2": "DMBT", "span1": [81, 85], "span2": [35, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9437": {"label": 3, "data": {"text": "PTP inhibition by hisphosphonates or vanadate was diminished by the metal chelating agent EDTA, or by the reducing agent dithiothreitol, suggesting that a metal ion and the oxidation of a cysteine residue are required for full inhibition.", "entity1": "PTP", "entity2": "hisphosphonates", "span1": [0, 3], "span2": [18, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4084": {"label": 9, "data": {"text": "Additionally, AIF levels in the cytosol decreased due to EGTA but not due to calpeptin.", "entity1": "AIF", "entity2": "calpeptin", "span1": [14, 17], "span2": [77, 86]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7389": {"label": 8, "data": {"text": "This is significant because superoxide production underlies the role of human PRODH in p53-mediated apoptosis, implying commonalities between eukaryotic and bacterial monofunctional PRODHs.", "entity1": "human PRODH", "entity2": "superoxide", "span1": [72, 83], "span2": [28, 38]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"15140": {"label": 8, "data": {"text": "The enzyme (TcCA) has a very high catalytic activity for the CO(2) hydration reaction, being similar kinetically to the human (h) isoform hCA II, although it is devoid of the His64 proton shuttle.", "entity1": "hCA II", "entity2": "CO(2)", "span1": [138, 144], "span2": [61, 66]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8195": {"label": 1, "data": {"text": "Resveratrol improves cardiomyopathy in dystrophin-deficient mice through SIRT1 protein-mediated modulation of p300 protein.", "entity1": "SIRT1", "entity2": "Resveratrol", "span1": [73, 78], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6209": {"label": 1, "data": {"text": "This study therefore characterized the binding of DF to the sigma receptors and NMDA-linked PCP sites and examined the anticonvulsant as well as locomotor effects of DF in mice in comparison with those of DM and DR. We found that DF, DM, and DR were relative high-affinity ligands at sigma-1 receptors (Ki=151, 205, 144 nM, respectively) while all of them were with low affinity at sigma-2 receptors (Ki=4-11 microM).", "entity1": "sigma-2 receptors", "entity2": "DF", "span1": [382, 399], "span2": [230, 232]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2163": {"label": 1, "data": {"text": "Similar to cocaine, other local anesthetics bind to the dopamine transporter (DAT) and inhibit DA uptake in rodent and monkey brain.", "entity1": "DAT", "entity2": "cocaine", "span1": [78, 81], "span2": [11, 18]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"10094": {"label": 8, "data": {"text": "The time course of PGE2 production was consistent with early release due to COX-1 activity followed by increased production 2-3 hours after surgery, consistent with COX-2 expression.", "entity1": "COX-1", "entity2": "PGE2", "span1": [76, 81], "span2": [19, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"3948": {"label": 3, "data": {"text": "In this study, uptake of phenformin and [(14)C]tetraethylammonium (TEA) and complex I inhibition by phenformin were examined in isolated liver and heart mitochondria.", "entity1": "complex I", "entity2": "phenformin", "span1": [76, 85], "span2": [100, 110]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15117": {"label": 2, "data": {"text": "Mn exposure (20\u00a0mg/kg) increased p38(MAPK) and Akt phosphorylation, but decreased DARPP-32-Thr-34 phosphorylation.", "entity1": "p38", "entity2": "Mn", "span1": [33, 36], "span2": [0, 2]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13209": {"label": 9, "data": {"text": "Triflusal (30 mg/kg) or aspirin treatment (30 mg/kg) did not reduce the levels of GFAP or Hsp27 immunostaining.", "entity1": "GFAP", "entity2": "Triflusal", "span1": [82, 86], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"4596": {"label": 3, "data": {"text": "Spiro heterocycles as potential inhibitors of SIRT1: Pd/C-mediated synthesis of novel N-indolylmethyl spiroindoline-3,2'-quinazolines.", "entity1": "SIRT1", "entity2": "N-indolylmethyl spiroindoline-3,2'-quinazolines", "span1": [46, 51], "span2": [86, 133]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6869": {"label": 3, "data": {"text": "Our results suggest that easing of Fas-triggered fulminant hepatitis by minocycline may involve a mitochondrial apoptotic pathway, probably through preventing cytochrome c release and thereby blocking downstream caspase activation.", "entity1": "cytochrome c", "entity2": "minocycline", "span1": [159, 171], "span2": [72, 83]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"893": {"label": 1, "data": {"text": "Here we compared the action of N(5)-substituted derivatives on recombinant rat neuronal nitric oxide synthase with their effects on dihydropteridine reductase (EC 1.6.99.7) and phenylalanine hydroxylase (EC 1.14.16.1),the well-studied classical H(4)biopterin-dependent reactions.", "entity1": "EC 1.14.16.1", "entity2": "N(5)", "span1": [204, 216], "span2": [31, 35]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10414": {"label": 1, "data": {"text": "CONCLUSIONS: Inhibition of PDE4 by rolipram unmasks beta(2)-adrenergic blockade of LTC(4) synthesis caused by FMLP/B.", "entity1": "beta(2)-adrenergic", "entity2": "rolipram", "span1": [52, 70], "span2": [35, 43]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"912": {"label": 1, "data": {"text": "Betaxolol inhibited specific [(3)H]-batrachotoxinin-A 20-alpha-benzoate ([(3)H]-BTX-B) binding to neurotoxin site 2 in a concentration-dependent manner with an IC(50) value of 9.8 microM.", "entity1": "neurotoxin site 2", "entity2": "[(3)H]-BTX-B", "span1": [98, 115], "span2": [73, 85]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"806": {"label": 2, "data": {"text": "Specifically, aniracetam, which potentiates wild-type AMPA receptors, is ineffective on the non-desensitizing GluR3(L507Y) mutant, but has synergistic effects with lithium on wild-type receptors.", "entity1": "L507Y", "entity2": "lithium", "span1": [116, 121], "span2": [164, 171]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1486": {"label": 1, "data": {"text": "Similarly, pretreatment with sulindac sulfide blocks the ability of EGF to induce ERK1/2 and Bad phosphorylation, but also down-regulates total Bad but not ERK1/2 protein levels.", "entity1": "ERK1/2", "entity2": "sulindac sulfide", "span1": [82, 88], "span2": [29, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"696": {"label": 1, "data": {"text": "To illuminate the controversy on alpha 1A- or alpha 1L-adrenoceptor involvement in noradrenaline-mediated contractions of rat small mesenteric artery (SMA), we have studied the effects of subtype-selective alpha 1-adrenoceptor agonists and antagonists under different experimental conditions.", "entity1": "alpha 1L-adrenoceptor", "entity2": "noradrenaline", "span1": [46, 67], "span2": [83, 96]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3634": {"label": 9, "data": {"text": "NaAsO(2) increased the mRNA levels of the light and medium subunits of neurofilament and decreased the mRNA levels of tau and tubulin in a dose-dependent manner; no significant effect was found in the mRNA levels of the heavy subunit of neurofilament, microtubule-associated protein 2, or actin.", "entity1": "microtubule-associated protein 2", "entity2": "NaAsO(2)", "span1": [252, 284], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9555": {"label": 1, "data": {"text": "Concanavalin A (Con A)-induced IFN-gamma, GM-CSF, and IL-3 mRNAs are dose-dependently inhibited by the nonselective betaAR agonist isoproterenol and by the selective beta2AR agonist fenoterol.", "entity1": "Concanavalin A", "entity2": "isoproterenol", "span1": [0, 14], "span2": [131, 144]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"14365": {"label": 3, "data": {"text": "The quinolizidine alkaloids (natural products) such as oxymatrine, sophoridine, sophocarpine and matrine carry the common molecular structure of O=C=N-C-C-C-N that possessed positive ionotropic effect and hERG blocking activity.", "entity1": "hERG", "entity2": "sophoridine", "span1": [205, 209], "span2": [67, 78]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 9]},
	"9083": {"label": 3, "data": {"text": "13cisRA and ROAc, but not 4HPR, caused a dose-dependent reduction in plasma osteocalcin, an effect that correlated with retinoid-induced bone effects.", "entity1": "osteocalcin", "entity2": "13cisRA", "span1": [76, 87], "span2": [0, 7]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"13037": {"label": 2, "data": {"text": "ATRA regulates gene expression via the activation of the retinoic acid receptor (RAR)alpha in human DCs, and RARalpha acutely regulates CD1d expression.", "entity1": "retinoic acid receptor (RAR)alpha", "entity2": "ATRA", "span1": [57, 90], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14577": {"label": 3, "data": {"text": "The selective SYK inhibitor P505-15 (PRT062607) inhibits B cell signaling and function in vitro and in vivo and augments the activity of fludarabine in chronic lymphocytic leukemia.", "entity1": "SYK", "entity2": "PRT062607", "span1": [14, 17], "span2": [37, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14149": {"label": 2, "data": {"text": "CONCLUSIONS AND IMPLICATIONS: In different cell systems, mianserin directly activates kappa-opioid receptors, displaying partial agonist activity at brain receptors.", "entity1": "kappa-opioid receptors", "entity2": "mianserin", "span1": [86, 108], "span2": [57, 66]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10765": {"label": 2, "data": {"text": "Inhibitors and neutralizing antibodies against heparin-binding epidermal growth factor-like growth factor (HB-EGF), and to a lesser extent transforming growth factor-alpha, reduced imatinib-mediated mitogen activated protein kinase (MAPK) activation.", "entity1": "MAPK", "entity2": "imatinib", "span1": [233, 237], "span2": [181, 189]}, "weak_labels": [-1, -1, -1, 1, -1, -1, 2, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15052": {"label": 8, "data": {"text": "The recent identification of zinc permeability of the lysosomal ion channel TRPML1 (transient receptor potential mucolipin 1), and the evidence of abnormal zinc levels in cells deficient in TRPML1, suggested a role for TRPML1\u00a0in zinc transport.", "entity1": "TRPML1", "entity2": "zinc", "span1": [76, 82], "span2": [29, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"13986": {"label": 1, "data": {"text": "Using a photo incorporable analogue of the general anesthetic, R(+)etomidate, we identified two transmembrane amino acids that were affinity labelled in purified bovine brain GABA(A)-R.", "entity1": "bovine brain GABA(A)-R", "entity2": "R(+)etomidate", "span1": [162, 184], "span2": [63, 76]}, "weak_labels": [0, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"166": {"label": 3, "data": {"text": "Acetylcholinesterase (AChE) inhibited by the organophosphate soman (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex.", "entity1": "Acetylcholinesterase", "entity2": "1,2,2-trimethyl-propylmethylphosphonofluoridate", "span1": [0, 20], "span2": [68, 115]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5275": {"label": 2, "data": {"text": "Nox4 oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific quinone derivatives could modulate this activity.", "entity1": "oxidase", "entity2": "quinone", "span1": [5, 12], "span2": [163, 170]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7278": {"label": 8, "data": {"text": "Transmembrane isoforms of adenylate cyclases (AC) integrate a wide variety of extracellular signals from neurotransmitters to morphogens and can also regulate cAMP production in response to calcium entry.", "entity1": "adenylate cyclases", "entity2": "cAMP", "span1": [26, 44], "span2": [159, 163]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"12050": {"label": 9, "data": {"text": "Here, we show that rTRPV1, rTRPV2, rTRPV3, and mTRPV4, as well as hTRPM8, and rTRPM3, which are expressed in dorsal root ganglion neurons, are insensitive toward apomorphine treatment.", "entity1": "hTRPM8", "entity2": "apomorphine", "span1": [66, 72], "span2": [162, 173]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9748": {"label": 4, "data": {"text": "In distinction to yohimbine, fluparoxan shows only modest partial agonist actions at h5-HT(1A) sites versus marked antagonist actions at halpha(2)-ARs.", "entity1": "h5-HT(1A)", "entity2": "fluparoxan", "span1": [85, 94], "span2": [29, 39]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1730": {"label": 1, "data": {"text": "Agonist competition assays with [3H]DHA showed the following rank order of potency: isoproterenol>epinephrine> norepinephrine, consistent with beta2AR interaction.", "entity1": "beta2AR", "entity2": "[3H]DHA", "span1": [143, 150], "span2": [32, 39]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3691": {"label": 2, "data": {"text": "8-pCPT-2'-O-Me-cAMP-AM potentiation of insulin secretion stimulated by tolbutamide was markedly inhibited by 2-APB (25 \u03bcM) and enhanced by the PKC inhibitor bisindolylmaleimide I (1 \u03bcM).", "entity1": "insulin", "entity2": "tolbutamide", "span1": [39, 46], "span2": [71, 82]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11164": {"label": 8, "data": {"text": "Recombinant PDE10A transfected and expressed in COS-7 cells hydrolyzed cAMP and cGMP with Km values of 0.26 and 7.2 microM, respectively, and Vmax with cGMP was almost twice that with cAMP.", "entity1": "PDE10A", "entity2": "cAMP", "span1": [12, 18], "span2": [184, 188]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13108": {"label": 1, "data": {"text": "There is a growing appreciation that the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway is organized to form transduction units that function to deliver specific messages.", "entity1": "PKA", "entity2": "cAMP", "span1": [97, 100], "span2": [73, 77]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11411": {"label": 3, "data": {"text": "Treatment with carvedilol is associated with a reversal of abnormal regulation of HIF-1alpha and VEGF in the failing ventricular myocardium.", "entity1": "HIF-1alpha", "entity2": "carvedilol", "span1": [82, 92], "span2": [15, 25]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8819": {"label": 3, "data": {"text": "Interestingly, SB203580, a selective inhibitor of p38 MAPK, blocked STIM1 phosphorylation and led to sustained STIM1-puncta formation and Ca2+ entry.", "entity1": "STIM1", "entity2": "SB203580", "span1": [68, 73], "span2": [15, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11891": {"label": 8, "data": {"text": "Cycloxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) has been shown to be important in esophageal tumorigenesis.", "entity1": "Cycloxygenase-2", "entity2": "prostaglandin E2", "span1": [0, 15], "span2": [32, 48]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14718": {"label": 3, "data": {"text": "Pharmacological inhibition of MTORC1 with rapamycin abrogated the insulin-induced phosphorylation of EIF4EBP1, RPS6KB1 and its downstream effector, RPS6.", "entity1": "RPS6KB1", "entity2": "rapamycin", "span1": [111, 118], "span2": [42, 51]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10082": {"label": 8, "data": {"text": "The specific activity of only ornithine aminotransferase (OAT), the rate-limiting enzyme in the conversion of ornithine to proline, increased in 2 weeks of hypertrophy.", "entity1": "ornithine aminotransferase", "entity2": "ornithine", "span1": [30, 56], "span2": [110, 119]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, 9]},
	"13997": {"label": 3, "data": {"text": "Cabozantinib (XL184) is a small-molecule kinase inhibitor with potent activity toward MET and VEGF receptor 2 (VEGFR2), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including RET, KIT, AXL, and FLT3.", "entity1": "receptor tyrosine kinases", "entity2": "Cabozantinib", "span1": [149, 174], "span2": [0, 12]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6165": {"label": 3, "data": {"text": "A case of therapy-related acute myeloblastic leukemia with t(16;21)(q24;q22) after chemotherapy with DNA-topoisomerase II inhibitors, etoposide and mitoxantrone, and the alkylating agent, cyclophosphamide.", "entity1": "DNA-topoisomerase II", "entity2": "mitoxantrone", "span1": [101, 121], "span2": [148, 160]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6974": {"label": 1, "data": {"text": "Recently, a G-protein-coupled receptor, termed GPR109A (HM74A in humans, PUMA-G in mice), was described and shown to mediate the nicotinic acid-induced antilipolytic effects in adipocytes.", "entity1": "HM74A", "entity2": "nicotinic acid", "span1": [56, 61], "span2": [129, 143]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8052": {"label": 2, "data": {"text": "Furthermore, metformin was able to not only decrease the paclitaxel-induced p38 MAPK-mediated ERCC1 expression, but also augment the cytotoxic effect induced by paclitaxel.", "entity1": "p38", "entity2": "paclitaxel", "span1": [76, 79], "span2": [57, 67]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"8661": {"label": 2, "data": {"text": "Our findings indicate that imatinib protects oocytes from cisplatin-induced cell death by inhibiting c-Abl kinase, which would otherwise activate TAp73-BAX-mediated apoptosis.", "entity1": "kinase", "entity2": "imatinib", "span1": [107, 113], "span2": [27, 35]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8077": {"label": 3, "data": {"text": "This study was designed to test the hypothesis that orlistat inhibits CESs with higher potency toward CES1 than CES2, a carboxylesterase with little lipase activity.", "entity1": "CES2", "entity2": "orlistat", "span1": [112, 116], "span2": [52, 60]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6902": {"label": 2, "data": {"text": "In vitro studies demonstrated that the retinoid X receptor (RXR) retinoid, bexarotene, at biologically relevant concentrations of 10(-6) M to 10(-8) M, upregulated both the p55 and p75 subunits of the IL-2R and enhanced 5- to 10-fold the susceptibility of T-cell leukemia cells to denileukin diftitox.", "entity1": "p55", "entity2": "bexarotene", "span1": [173, 176], "span2": [75, 85]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4027": {"label": 3, "data": {"text": "Central and peripheral administration of kisspeptin stimulates the hypothalamic-pituitary-gonadal (HPG) axis whilst pre-administration of a gonadotrophin releasing hormone (GnRH) antagonist abolishes this effect.", "entity1": "kisspeptin", "entity2": "GnRH", "span1": [41, 51], "span2": [173, 177]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12544": {"label": 2, "data": {"text": "In plasma membranes prepared from these isolated brown fat cells by borate extraction there was a similar enrichment of activity of SSAO and of the plasma membrane marker enzyme, phosphodiesterase I.", "entity1": "SSAO", "entity2": "borate", "span1": [132, 136], "span2": [68, 74]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12430": {"label": 8, "data": {"text": "It is possible that variations in cytochrome P450 3A enzyme-mediated metabolism of BDP may contribute to this phenomenon.", "entity1": "cytochrome P450 3A", "entity2": "BDP", "span1": [34, 52], "span2": [83, 86]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10432": {"label": 0, "data": {"text": "Formation of pyruvate by SDH is a two-step reaction in which the hydroxyl group of serine is cleaved to produce aminoacrylate, and then the aminoacrylate is deaminated by nonenzymatic hydrolysis to produce pyruvate.", "entity1": "SDH", "entity2": "serine", "span1": [25, 28], "span2": [83, 89]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"13608": {"label": 0, "data": {"text": "The key difference in structure of Lp(a) and plasminogen is replacement of Arg with Ser at position 560.", "entity1": "plasminogen", "entity2": "Ser", "span1": [45, 56], "span2": [84, 87]}, "weak_labels": [-1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1815": {"label": 8, "data": {"text": "In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit human Na(V)1.5 sodium channels expressed in Chinese Hamster Ovary (CHO-K1) cells.", "entity1": "human Na(V)1.5", "entity2": "sodium", "span1": [135, 149], "span2": [150, 156]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9920": {"label": 1, "data": {"text": "Serotonin transporter gene regulatory region polymorphism (5-HTTLPR), [3H]paroxetine binding in healthy control subjects and alcohol-dependent patients and their relationships to impulsivity.", "entity1": "Serotonin transporter", "entity2": "[3H]paroxetine", "span1": [0, 21], "span2": [70, 84]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"4414": {"label": 6, "data": {"text": "NCFP binds to the CPPHA site on mGlu5 and potentiates mGlu5-mediated responses in both recombinant and native systems.", "entity1": "mGlu5", "entity2": "CPPHA", "span1": [32, 37], "span2": [18, 23]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6512": {"label": 3, "data": {"text": "Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril.", "entity1": "Angiotensin II", "entity2": "Aliskiren", "span1": [0, 14], "span2": [74, 83]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5127": {"label": 3, "data": {"text": "Pyrrolidine dithiocarbamate (PDTC), a specific NF-\u03baB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-\u03baB activity.", "entity1": "iNOS", "entity2": "PDTC", "span1": [142, 146], "span2": [29, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2808": {"label": 3, "data": {"text": "Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS.", "entity1": "E-selectin", "entity2": "1400W dihydrochloride", "span1": [186, 196], "span2": [96, 117]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"799": {"label": 1, "data": {"text": "Specifically, aniracetam, which potentiates wild-type AMPA receptors, is ineffective on the non-desensitizing GluR3(L507Y) mutant, but has synergistic effects with lithium on wild-type receptors.", "entity1": "AMPA receptors", "entity2": "lithium", "span1": [54, 68], "span2": [164, 171]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6480": {"label": 2, "data": {"text": "Reactivation potentials of BuChE (the difference between oxime-reactivated and -unreactivated enzyme activity) declined significantly with time after organophosphate ingestion.", "entity1": "BuChE", "entity2": "oxime", "span1": [27, 32], "span2": [57, 62]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13597": {"label": 5, "data": {"text": "Desvenlafaxine succinate (DVS) is a recently introduced antagonist of the human norepinephrine and serotonin transporters (hNET and hSERT, respectively), currently in clinical development for use in the treatment of major depressive disorder and vasomotor symptoms associated with menopause.", "entity1": "hNET", "entity2": "Desvenlafaxine succinate", "span1": [123, 127], "span2": [0, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"6862": {"label": 2, "data": {"text": "Pre-irradiation administration of RP-1 enhanced levels of GSH induced increase in complex I (upto 16 h), complex I/III (4 h) complex II/III activity (upto 24 h; p < 0.01) and inhibited the radiation-induced decrease in MMP significantly (24 h; p < 0.01).", "entity1": "complex I", "entity2": "GSH", "span1": [82, 91], "span2": [58, 61]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5886": {"label": 0, "data": {"text": "Using a similar procedure to analyze ODC labeled by reaction with [5-14C]DFMO, it was found that lysine 69 and cysteine 360 formed covalent adducts with the inhibitor.", "entity1": "ODC", "entity2": "cysteine", "span1": [37, 40], "span2": [111, 119]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12260": {"label": 1, "data": {"text": "Isothiocyanates, thought to be responsible for the chemopreventive properties of this food group, are conjugated to glutathione by glutathione S-transferases (GSTs) before urinary excretion.", "entity1": "GSTs", "entity2": "Isothiocyanates", "span1": [159, 163], "span2": [0, 15]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13871": {"label": 1, "data": {"text": "Here, we report that the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) is essential for coupling ibuprofen to RhoA inhibition and subsequent neurite growth promotion in neurons.", "entity1": "peroxisome proliferator-activated receptor gamma", "entity2": "ibuprofen", "span1": [46, 94], "span2": [133, 142]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12071": {"label": 0, "data": {"text": "Cysteine 360, which was the major adduct accounting for about 90% of the total labeling, is contained within the sequence -WGPTCDGL(I)D-, which is present in all known eukaryote ODCs.", "entity1": "WGPTCDGL(I)D", "entity2": "Cysteine", "span1": [123, 135], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7797": {"label": 4, "data": {"text": "Reversal of inhibition by D2 agonist quinpirole was produced by serotonin (50 \u00b5M) and by neurotensin (5-10 nM).", "entity1": "D2", "entity2": "quinpirole", "span1": [26, 28], "span2": [37, 47]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"1349": {"label": 1, "data": {"text": "A series of mazindol (2) and homomazindol (3) analogues with a variety of electron-donating and electron-withdrawing groups in the pendant aryl group and the benzo ring C, as well as H, methoxy, and alkyl groups replacing the hydroxyl group were synthesized, and their binding affinities at the dopamine transporter (DAT) on rat or guinea pig striatal membranes were determined.", "entity1": "DAT", "entity2": "mazindol", "span1": [317, 320], "span2": [12, 20]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"8275": {"label": 8, "data": {"text": "CYP2B6 inhibition reduces methadone N-demethylation and clearance, and alters methadone concentrations, demonstrating an important role for CYP2B6 in clinical methadone disposition.", "entity1": "CYP2B6", "entity2": "methadone", "span1": [140, 146], "span2": [159, 168]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15499": {"label": 1, "data": {"text": "The current reduction we found at higher pBQN concentrations was a cysteine-dependent desensitization of TRPA1, and did not require prior activation.", "entity1": "TRPA1", "entity2": "pBQN", "span1": [105, 110], "span2": [41, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"772": {"label": 0, "data": {"text": "Flecainide block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the long QT syndrome 3 (LQT3) sodium channel alpha subunit mutation with three amino acids deleted (DeltaKPQ) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings.", "entity1": "long QT syndrome 3 (LQT3) sodium channel alpha", "entity2": "amino acids", "span1": [84, 130], "span2": [159, 170]}, "weak_labels": [0, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8251": {"label": 0, "data": {"text": "N-terminal sequencing indicated that pro-BMP-2 was cleaved by FSAP at the canonical PC cleavage site, giving rise to mature BMP-2 (Arg(282)\u2193Gln(283)), as well as in the N-terminal heparin binding region of mature BMP-2, generating a truncated mature BMP-2 peptide (Arg(289)\u2193Lys(290)).", "entity1": "BMP-2", "entity2": "Gln", "span1": [124, 129], "span2": [140, 143]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13690": {"label": 2, "data": {"text": "Two imidazoquinoline molecules, imiquimod and gardiquimod, markedly activated both porcine TLR7 and TLR8 whereas only human TLR7, but not TLR8, was activated by the ligands.", "entity1": "TLR8", "entity2": "imidazoquinoline", "span1": [100, 104], "span2": [4, 20]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"6986": {"label": 1, "data": {"text": "RATIONALE: Several drugs used to treat bipolar disorder (lithium and carbamazepine), when administered chronically to rats, reduce the turnover of arachidonic acid, but not docosahexaenoic acid, in brain phospholipids by decreasing the activity of an arachidonic acid-selective phospholipase A(2).", "entity1": "phospholipase A(2)", "entity2": "arachidonic acid", "span1": [278, 296], "span2": [251, 267]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7583": {"label": 8, "data": {"text": "threo-methylphenidate inhibits the dopamine transporter and the norepinephrine transporter, resulting in elevations of these monoamines after impulse release.", "entity1": "norepinephrine transporter", "entity2": "monoamines", "span1": [64, 90], "span2": [125, 135]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"6010": {"label": 3, "data": {"text": "CONCLUSIONS: Nabumetone does dose-dependently inhibit the cyclooxygenase activity of platelet PGHS-1 of healthy subjects both in vivo and ex vivo.", "entity1": "cyclooxygenase", "entity2": "Nabumetone", "span1": [58, 72], "span2": [13, 23]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3730": {"label": 3, "data": {"text": "The present results indicated that N-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways.", "entity1": "MEK", "entity2": "BPs", "span1": [228, 231], "span2": [37, 40]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6872": {"label": 2, "data": {"text": "placebo; n=24 animals in each group]; 2) neutrophil sequestration in the pancreas [pancreatic myeloperoxidase oxidase (MPO) activity (fold increase over control) (prophylactic treatment: placebo, 5.78+/-0.63; PAG, 2.97+/-0.39; therapeutic treatment: placebo, 5.48+/-0.52; PAG, 3.03+/-0.47; P<0.05 PAG c.f.", "entity1": "myeloperoxidase oxidase", "entity2": "PAG", "span1": [94, 117], "span2": [209, 212]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15050": {"label": 1, "data": {"text": "The iodido complexes retain potency in p53 mutant colon cells.", "entity1": "p53", "entity2": "iodido", "span1": [39, 42], "span2": [4, 10]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2498": {"label": 3, "data": {"text": "Licofelone, a dual anti-inflammatory drug that inhibits 5-lipoxygenase (LOX) and cyclooxygenase (COX) enzymes, may have a better cardiovascular profile that cycloxygenase-2 inhibitors due to cycloxygenase-1 blockade-mediated antithrombotic effect and a better gastrointestinal tolerability.", "entity1": "COX", "entity2": "Licofelone", "span1": [97, 100], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10855": {"label": 3, "data": {"text": "Imatinib (STI571, Gleevec, Glivec; Novartis Pharmaceuticals, East Hanover, NJ), a selective inhibitor of KIT, ABL, BCR-ABL, PDGFRA, and PDGFRB, represents a new paradigm of targeted cancer therapy and has revolutionized the treatment of patients with chronic myelogenous leukemia and GISTs.", "entity1": "PDGFRB,", "entity2": "Glivec", "span1": [136, 143], "span2": [27, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13132": {"label": 2, "data": {"text": "CONCLUSION(S): Short-term exposure of mifepristone in new starters of DMPA increases the expression of endometrial ERalpha, PRAB, PRB, and SRC-1 and promotes cell proliferation.", "entity1": "ERalpha", "entity2": "mifepristone", "span1": [115, 122], "span2": [38, 50]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4225": {"label": 3, "data": {"text": "The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) PhIP (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control.", "entity1": "SOD", "entity2": "PhIP", "span1": [189, 192], "span2": [118, 122]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14354": {"label": 3, "data": {"text": "mRNA levels of receptor activator of nuclear factor kappa-B (RANK), its ligand RANKL, tumor necrosis factor alpha (TNF-\u03b1) and RANKL/osteoprotegerin (OPG) ratio were diminished in the periodontium of CCL3(-/-) mice and in the group treated with Met-RANTES.", "entity1": "osteoprotegerin", "entity2": "Met", "span1": [132, 147], "span2": [244, 247]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"908": {"label": 1, "data": {"text": "In this study, we examined whether betaxolol and other beta-adrenoceptor antagonists interact directly with neurotoxin binding to sites 1 and 2 of the voltage-sensitive sodium channel (Na(+) channel) in rat cerebrocortical synaptosomes.", "entity1": "voltage-sensitive sodium channel", "entity2": "betaxolol", "span1": [151, 183], "span2": [35, 44]}, "weak_labels": [-1, -1, -1, 1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"283": {"label": 4, "data": {"text": "Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors.", "entity1": "beta 2-adrenoceptor", "entity2": "salbutamol", "span1": [86, 105], "span2": [114, 124]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"572": {"label": 2, "data": {"text": "These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by Tomudex and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in cyclin E and cdk2 kinase activities.", "entity1": "cdk2", "entity2": "Tomudex", "span1": [256, 260], "span2": [127, 134]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11003": {"label": 1, "data": {"text": "In this study, antidepressants with selectivity for the noradrenaline transporter (reboxetine and desipramine), or the serotonin transporter (fluoxetine and clomipramine) were examined in terms of their ability to promote an anti-inflammatory cytokine phenotype in human blood.", "entity1": "noradrenaline transporter", "entity2": "desipramine", "span1": [56, 81], "span2": [98, 109]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, 9]},
	"3686": {"label": 2, "data": {"text": "Tolbutamide and gliclazide block the K(ATP) channel K(ir)6.2/Sur1, causing membrane depolarization and stimulating insulin secretion in pancreatic beta cells.", "entity1": "insulin", "entity2": "Tolbutamide", "span1": [115, 122], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8303": {"label": 1, "data": {"text": "Both myosin-18A isoforms bound N-methylanthraniloyl-nucleotides, but the rate of ATP hydrolysis was very slow (<0.002 s(-1)) and not significantly enhanced by actin.", "entity1": "myosin-18A", "entity2": "N-methylanthraniloyl-nucleotides", "span1": [5, 15], "span2": [31, 63]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"5863": {"label": 1, "data": {"text": "To our surprise, when mu-receptor binding was determined by using [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO), a 10-15% decrease in binding was also observed in the midbrain and cortex after 4 days of DPDPE treatment.", "entity1": "mu-receptor", "entity2": "[3H]Tyr-D-Ala-Gly-MePhe-Gly-ol", "span1": [22, 33], "span2": [66, 96]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12438": {"label": 6, "data": {"text": "While SAR within the HTS series was very shallow and unable to be optimized, grafting the phenethyl ether linkage onto the ML129/ML172 cores led to the first sub-micromolar M5 PAM, ML326 (VU0467903), (human and rat M5 EC50s of 409nM and 500nM, respectively) with excellent mAChR selectivity (M1-M4 EC50s >30\u03bcM) and a robust 20-fold leftward shift of the ACh CRC.", "entity1": "M5", "entity2": "VU0467903", "span1": [215, 217], "span2": [188, 197]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2230": {"label": 1, "data": {"text": "Computer modeling suggests that the KITD816V mutation destabilizes the inactive conformation of the KIT activation loop to which imatinib binds, but it is not predicted to impair binding of KIT by dasatinib.", "entity1": "KIT", "entity2": "dasatinib", "span1": [36, 39], "span2": [197, 206]}, "weak_labels": [-1, -1, 0, 1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7264": {"label": 3, "data": {"text": "Some clinically used compounds, such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, sulpiride, and indisulam, or the orphan drug benzolamide, showed effective hCA VI inhibitory activity, with inhibition constants of 0.8-79 nM.", "entity1": "hCA VI", "entity2": "methazolamide", "span1": [218, 224], "span2": [55, 68]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10077": {"label": 3, "data": {"text": "Salicylates inhibited ATPase activity stimulated by this specific heptapeptide but did not block ATP binding or induce BiP expression.", "entity1": "ATPase", "entity2": "Salicylates", "span1": [22, 28], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7539": {"label": 3, "data": {"text": "Phenelzine (PLZ), a nonselective irreversible inhibitor of monoamine oxidase (MAO), also inhibits GABA-transaminase (GABA-T), markedly increasing brain GABA levels.", "entity1": "monoamine oxidase", "entity2": "Phenelzine", "span1": [59, 76], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12375": {"label": 8, "data": {"text": "This shows that CPT2 and CACT are crucial for mitochondrial acylcarnitine formation and export to the extracellular fluids in mFAOD.-Violante, S., IJlst, L., te Brinke, H., Tavares de Almeida, I., Wanders, R. J.", "entity1": "CACT", "entity2": "acylcarnitine", "span1": [25, 29], "span2": [60, 73]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13236": {"label": 2, "data": {"text": "EGTA and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid tetrakis (BAPTA), two Ca2+ chelators, but not nifedipine, an L-type Ca2+ channel blocker, prevented GRIP1 degradation.", "entity1": "GRIP1", "entity2": "1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid tetrakis", "span1": [167, 172], "span2": [9, 75]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"13810": {"label": 3, "data": {"text": "Others kinase inhibitors used recently in cancer therapy include Dasatinib (BMS-354825) specific for ABL non-receptor cytoplasmic kinase, Gefitinib (Iressa), Erlotinib (OSI-774, Tarceva) and Sunitinib (SU 11248, Sutent) specific for VEGF receptor kinase, AMN107 (Nilotinib) and INNO-406 (NS-187) specific for c-KIT kinase.", "entity1": "VEGF receptor", "entity2": "Iressa", "span1": [233, 246], "span2": [149, 155]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"440": {"label": 9, "data": {"text": "Epinastine (100 microM) did not displace the dose-response curve to exogenously applied substance P (0.01-10 microM).", "entity1": "substance P", "entity2": "Epinastine", "span1": [88, 99], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1735": {"label": 1, "data": {"text": "beta2AR density measured with [3H]dihydroalprenolol ([3H]DHA) increased either 13- or 77-fold in infected cells compared to mock infected controls depending on the culture conditions used.", "entity1": "beta2AR", "entity2": "[3H]DHA", "span1": [0, 7], "span2": [53, 60]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14693": {"label": 3, "data": {"text": "This work investigated the drug interaction potential of GSK1292263, a novel GPR119 agonist, with the HMG-coA reductase inhibitors simvastatin and rosuvastatin.", "entity1": "HMG-coA reductase", "entity2": "rosuvastatin", "span1": [102, 119], "span2": [147, 159]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, 3, 3, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11142": {"label": 1, "data": {"text": "FGFs signal through transmembrane receptor tyrosine kinases, but heparan sulfate is also required for signaling by members of the FGF family.", "entity1": "FGF", "entity2": "sulfate", "span1": [130, 133], "span2": [73, 80]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15154": {"label": 1, "data": {"text": "We hypothesized that CREB is activated by a distinct signaling pathway in response to pulsatile GnRH in a frequency-dependent manner to dictate the FSH\u03b2 transcriptional response.", "entity1": "FSH\u03b2", "entity2": "GnRH", "span1": [148, 152], "span2": [96, 100]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12334": {"label": 8, "data": {"text": "Cultured rat DRG neurons endogenously expressed rCtr1 protein on their neuronal cell body plasma membranes and cytoplasm, and displayed substantial capacity for taking up copper, but were resistant to copper toxicity.", "entity1": "rCtr1", "entity2": "copper", "span1": [48, 53], "span2": [171, 177]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8397": {"label": 2, "data": {"text": "MeHg significantly increased DA precursor accumulation in cells treated with 3-hydroxybenzylhydrazine (10\u00b5M), revealing that MeHg increases tyrosine hydroxylase activity.", "entity1": "tyrosine hydroxylase", "entity2": "MeHg", "span1": [140, 160], "span2": [125, 129]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9050": {"label": 1, "data": {"text": "Chlorpromazine, levomepromazine, and their metabolites had 5-30 times higher binding affinities for muscarinic cholinergic receptors than fluphenazine, perphenazine and their metabolites.", "entity1": "muscarinic cholinergic receptors", "entity2": "levomepromazine", "span1": [100, 132], "span2": [16, 31]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8626": {"label": 1, "data": {"text": "In contrast, activation of Nrf2 by sulforaphane and tert-butylhydroquinone depend upon Keap1-C151 and not p62 (the canonical mechanism).", "entity1": "Keap1", "entity2": "sulforaphane", "span1": [87, 92], "span2": [35, 47]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9795": {"label": 3, "data": {"text": "Another inhibitor, brequinar was previously reported to be a slow-binding inhibitor of the human dihydroorotate dehydrogenase [W. Knecht, M. Loffler, Species-related inhibition of human and rat dihyroorotate dehydrogenase by immunosuppressive isoxazol and cinchoninic acid derivatives, Biochem.", "entity1": "human dihydroorotate dehydrogenase", "entity2": "brequinar", "span1": [91, 125], "span2": [19, 28]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"2578": {"label": 2, "data": {"text": "Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and HDC mRNA induced by TDI in TDI-sensitized rats.", "entity1": "HDC", "entity2": "TDI", "span1": [140, 143], "span2": [160, 163]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"417": {"label": 1, "data": {"text": "RS 17053 showed high affinity and selectivity for alpha 1A adrenoceptors (pKi 8.6) relative to alpha 1B (pKi = 7.3) and alpha 1D (pKi = 7.1) subtypes.", "entity1": "alpha 1D", "entity2": "RS 17053", "span1": [120, 128], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"463": {"label": 3, "data": {"text": "(+/-)-Tamsulosin effectively antagonized the positive inotropic effect of phenylephrine even after inactivation of alpha 1B-adrenoceptors by treatment with chlorethylclonidine, which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine.", "entity1": "alpha 1B-adrenoceptors", "entity2": "chlorethylclonidine", "span1": [115, 137], "span2": [156, 175]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"15493": {"label": 0, "data": {"text": "We used whole-cell recordings of human embryonic kidney cells heterologously expressing either wild-type TRPA1 or TRPA1 with three serine-substituted cysteines crucial for electrophile activation (C621S, C641S, C665S).", "entity1": "C621S", "entity2": "cysteines", "span1": [197, 202], "span2": [150, 159]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"129": {"label": 3, "data": {"text": "The cAMP phosphodiesterase was inhibited completely by felodipine and the p-chloro analogue with IC50 values of 3.7 and 1.5 microM respectively.", "entity1": "cAMP phosphodiesterase", "entity2": "felodipine", "span1": [4, 26], "span2": [55, 65]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13444": {"label": 1, "data": {"text": "The inhibitory effects of GW9662 and T0070907 (PPARgamma antagonists), on COX-2 expression and on stimulation of COX-2 promoter activity by EPA and GLA suggest that PPARgamma is implicated in COX-2 induction.", "entity1": "COX-2 promoter", "entity2": "T0070907", "span1": [113, 127], "span2": [37, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4299": {"label": 8, "data": {"text": "Compound 6 stimulated OATP1B3-mediated estradiol 17\u03b2-glucuronide uptake by increasing the apparent affinity of OATP1B3 for its substrate.", "entity1": "OATP1B3", "entity2": "estradiol 17\u03b2-glucuronide", "span1": [22, 29], "span2": [39, 64]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"15243": {"label": 3, "data": {"text": "Furthermore, silymarin, silybin A, and silybin B (100 \u00b5M) significantly inhibited OATP-mediated estradiol-17\u03b2-glucuronide and rosuvastatin uptake into human hepatocytes.", "entity1": "OATP", "entity2": "silybin A", "span1": [82, 86], "span2": [24, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13230": {"label": 1, "data": {"text": "Our results suggest that glutamate induces GRIP1 degradation by proteasome through an NMDA receptor-Ca2+ pathway and that GRIP1 degradation may play an important role in regulating GluR2 surface expression.", "entity1": "NMDA receptor", "entity2": "glutamate", "span1": [86, 99], "span2": [25, 34]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1770": {"label": 1, "data": {"text": "We have adenovirally overexpressed beta(1)-adrenoceptors in isolated, cultured adult rat ventricular cardiomyocytes and observed the inotropic potency of isoprenaline and CGP 12177A (in the presence of 1 microm propranolol).", "entity1": "beta(1)-adrenoceptors", "entity2": "isoprenaline", "span1": [35, 56], "span2": [154, 166]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"7224": {"label": 1, "data": {"text": "In this setting there is a GnRH-induced association and nuclear translocation of the androgen receptor with Hic-5.", "entity1": "Hic-5", "entity2": "GnRH", "span1": [108, 113], "span2": [27, 31]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5626": {"label": 8, "data": {"text": "BACKGROUND: Norepinephrine transporter (NET) is involved in the regulation of norepinephrine (NE) turnover and metabolism.", "entity1": "Norepinephrine transporter", "entity2": "norepinephrine", "span1": [12, 38], "span2": [78, 92]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"5949": {"label": 1, "data": {"text": "Pimozide and thioridazine had no effect on the estradiol binding properties of the MCF-7 ER, nor did pimozide interfere with the induction of progesterone receptors by estradiol.", "entity1": "progesterone receptors", "entity2": "estradiol", "span1": [142, 164], "span2": [168, 177]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4475": {"label": 3, "data": {"text": "Our findings indicate that catalpol suppresses AGE-mediated inflammation by inhibiting ROS production and NF-\u03baB activity.", "entity1": "NF-\u03baB", "entity2": "catalpol", "span1": [106, 111], "span2": [27, 35]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"8471": {"label": 1, "data": {"text": "Of the new compounds, Dmt(1)-(R)-\u03b2Pro(2)-Trp(3)-(2-furyl)Map(4) (analogue 12) displayed the highest affinity toward MOR, in the picomolar range (Ki(\u03bc) = 3.72 pM).", "entity1": "MOR", "entity2": "Dmt", "span1": [116, 119], "span2": [22, 25]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2742": {"label": 3, "data": {"text": "Preclinical pharmacokinetics and in vitro metabolism of dasatinib (BMS-354825): a potent oral multi-targeted kinase inhibitor against SRC and BCR-ABL.", "entity1": "ABL", "entity2": "dasatinib", "span1": [146, 149], "span2": [56, 65]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3251": {"label": 1, "data": {"text": "The other endogenous steroids, androstenedione (ANE) and dihydrotestosterone (DHT), had considerably lower hAR transport rates.", "entity1": "hAR", "entity2": "androstenedione", "span1": [107, 110], "span2": [31, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"8088": {"label": 2, "data": {"text": "E235 also activated DNA damage response signaling, resulting in increased levels of Ser15-phosphorylated p53, \u03b3-H2AX, and phosphorylated checkpoint kinase 2 (Chk2), although E235 does not appear to cause physical DNA damage.", "entity1": "\u03b3-H2AX", "entity2": "E235", "span1": [110, 116], "span2": [0, 4]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"9064": {"label": 1, "data": {"text": "Their histamine H1 receptor binding affinities indicate that metabolites may contribute to the sedative effects of chlorpromazine and levomepromazine.", "entity1": "histamine H1 receptor", "entity2": "chlorpromazine", "span1": [6, 27], "span2": [115, 129]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4850": {"label": 3, "data": {"text": "The ROS scavenger N-acetyl l-cysteine and the mitochondrial antioxidant Mito-TEMPO rescued the inhibitory effect of cucurbitacin I on Rac1 activation.", "entity1": "Rac1", "entity2": "cucurbitacin I", "span1": [134, 138], "span2": [116, 130]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15438": {"label": 3, "data": {"text": "The procedure was to reduce liver AOX activity by providing tungsten or hydralazine in the drinking water or to use the AOX-deficient DBA/2 mouse strain.", "entity1": "AOX", "entity2": "hydralazine", "span1": [34, 37], "span2": [72, 83]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4777": {"label": 9, "data": {"text": "We show that CIQ does not bind to the amino-terminal domain of the NMDA receptor and does not share structural determinants with modulators acting at the agonist-binding domain dimer interface or ion channel pore.", "entity1": "NMDA receptor", "entity2": "CIQ", "span1": [67, 80], "span2": [13, 16]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, 6, -1, -1, -1, -1, -1, -1, -1, 9]},
	"6367": {"label": 4, "data": {"text": "The related piperidines ohmefentanyl and sufentanil and the nonselective opioid receptor agonist etorphine were less potent nociceptin receptor agonists.", "entity1": "opioid receptor", "entity2": "etorphine", "span1": [73, 88], "span2": [97, 106]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7464": {"label": 8, "data": {"text": "The mechanisms that specify the vesicular phenotype of inhibitory interneurons in vertebrates are poorly understood because the two main inhibitory transmitters, glycine and GABA, share the same vesicular inhibitory amino acid transporter (VIAAT) and are both present in neurons during postnatal development.", "entity1": "vesicular inhibitory amino acid transporter", "entity2": "GABA", "span1": [195, 238], "span2": [174, 178]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, 9]},
	"7695": {"label": 3, "data": {"text": "Fenoldopam also inhibited insulin receptor mRNA and protein expression, which was time dependent and concentration dependent.", "entity1": "insulin receptor", "entity2": "Fenoldopam", "span1": [26, 42], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13237": {"label": 2, "data": {"text": "EGTA and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid tetrakis (BAPTA), two Ca2+ chelators, but not nifedipine, an L-type Ca2+ channel blocker, prevented GRIP1 degradation.", "entity1": "GRIP1", "entity2": "BAPTA", "span1": [167, 172], "span2": [77, 82]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"14576": {"label": 3, "data": {"text": "The selective SYK inhibitor P505-15 (PRT062607) inhibits B cell signaling and function in vitro and in vivo and augments the activity of fludarabine in chronic lymphocytic leukemia.", "entity1": "SYK", "entity2": "P505-15", "span1": [14, 17], "span2": [28, 35]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3160": {"label": 0, "data": {"text": "Kinases, including IKKbeta, JNK, ERK, mTOR, and S6K, activated by the inducers of insulin resistance induce uncontrolled IRS serine phosphorylation.", "entity1": "IRS", "entity2": "serine", "span1": [121, 124], "span2": [125, 131]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9909": {"label": 2, "data": {"text": "4-chloro-6-[(2,3-xylidine)-pirimidinylthio] acetic acid (WY-14,643), a specific ligand of the PPAR-alpha subtype, causes the most dramatic increase in UCP-3 mRNA, whereas troglitazone, a specific activator of PPAR-gamma, also significantly increases UCP-3 mRNA abundance in skeletal muscle of lactating mice.", "entity1": "PPAR-gamma", "entity2": "troglitazone", "span1": [209, 219], "span2": [171, 183]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7882": {"label": 3, "data": {"text": "Antiretroviral protease inhibitors lopinavir (LPV) and ritonavir (RTV) are reported BSEP inhibitors.", "entity1": "BSEP", "entity2": "ritonavir", "span1": [84, 88], "span2": [55, 64]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"697": {"label": 1, "data": {"text": "Selective protection of a putative alpha 1A-adrenoceptor population against the irreversible action of phenoxybenzamine also failed to increase the potency of RS-17053 (pA2 = 8.25 +/- 0.06 against A61603).", "entity1": "alpha 1A-adrenoceptor", "entity2": "phenoxybenzamine", "span1": [35, 56], "span2": [103, 119]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3494": {"label": 3, "data": {"text": "A significant decrease of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH) activities and glutathione (GSH) levels and an increase of malondialdehyde (MDA) quantity was observed after CCl4 and PC administration alone.", "entity1": "aspartate aminotransferase", "entity2": "CCl4", "span1": [26, 52], "span2": [217, 221]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"13642": {"label": 1, "data": {"text": "Top1p is the cellular target of the anti-cancer drug camptothecin (CPT), which reversibly stabilizes a covalent enzyme-DNA intermediate.", "entity1": "Top1p", "entity2": "camptothecin", "span1": [0, 5], "span2": [53, 65]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4341": {"label": 3, "data": {"text": "Pinosylvin was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3\u03b2 (GSK-3\u03b2) signaling pathway.", "entity1": "PI3K", "entity2": "Pinosylvin", "span1": [198, 202], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"424": {"label": 1, "data": {"text": "Data in this study suggest that the alpha 1 adrenoceptor mediating noradrenaline-induced contractions of human prostate, whilst having some of the characteristics of an alpha 1A adrenoceptor, cannot be satisfactorily aligned with cloned alpha 1A, alpha 1B or alpha 1D adrenoceptors.", "entity1": "alpha 1 adrenoceptor", "entity2": "noradrenaline", "span1": [36, 56], "span2": [67, 80]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3278": {"label": 3, "data": {"text": "Phenothiazines inhibit S100A4 function by inducing protein oligomerization.", "entity1": "S100A4", "entity2": "Phenothiazines", "span1": [23, 29], "span2": [0, 14]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"4780": {"label": 9, "data": {"text": "The activity of CYP3A in excised liver samples from rats following multiple baicalin treatment was significantly decreased compared to that of the control group (P<0.05), whereas multiple doses of baicalin had no obvious effect on the activity of CYP2D.", "entity1": "CYP2D", "entity2": "baicalin", "span1": [247, 252], "span2": [197, 205]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7963": {"label": 0, "data": {"text": "A domain in the carboxy-terminus of TSPO was identified and characterized as the cholesterol recognition/interaction amino acid consensus (CRAC).", "entity1": "TSPO", "entity2": "amino acid", "span1": [36, 40], "span2": [117, 127]}, "weak_labels": [0, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13860": {"label": 3, "data": {"text": "As discussed in this review, various progestogens including dydrogesterone and its 20alpha-dihydro-derivative, medrogestone, promegestone, nomegestrol acetate and norelgestromin can reduce intratissular levels of estradiol in breast cancer by blocking sulfatase and 17beta-hydroxysteroid-dehydrogenase type 1 activities.", "entity1": "17beta-hydroxysteroid-dehydrogenase type 1", "entity2": "medrogestone", "span1": [266, 308], "span2": [111, 123]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8497": {"label": 9, "data": {"text": "Furthermore, the (22R)-spirosolanol glycoside (11) selectively induced apoptosis in A549 cells without affecting the caspase-3 activity level.", "entity1": "caspase-3", "entity2": "(22R)-spirosolanol glycoside", "span1": [117, 126], "span2": [17, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5507": {"label": 4, "data": {"text": "In pigeons trained to discriminate 1.7 mg/kg dezocine from saline, a series of opioids with activity at the mu opioid receptor substituted completely for the dezocine stimulus with a rank order of potency similar to that obtained in other assays sensitive to the effects of mu agonists (i.e., fentanyl >[-]-cyclazocine >buprenorphine = butorphanol >l-methadone >nalbuphine >[-]-metazocine >morphine).", "entity1": "mu opioid receptor", "entity2": "butorphanol", "span1": [108, 126], "span2": [336, 347]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9713": {"label": 1, "data": {"text": "Activity of the mutant delta-aminolevulinate synthase protein expressed in vitro was 15.1% compared with the normal control, but was increased up to 34.5% by the addition of pyridoxal 5'-phosphate, consistent with the clinical response of the patient to pyridoxine treatment.", "entity1": "delta-aminolevulinate synthase", "entity2": "pyridoxine", "span1": [23, 53], "span2": [254, 264]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5308": {"label": 8, "data": {"text": "Introduction: 5-Lipoxygenase (5-LO) is a crucial enzyme of the arachidonic acid (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) with the help of FLAP, the 5-LO-activating protein.", "entity1": "5-Lipoxygenase", "entity2": "arachidonic acid", "span1": [14, 28], "span2": [63, 79]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]},
	"716": {"label": 0, "data": {"text": "The dimeric C-terminal deletion mutant (Delta473-528) of hTH1 also showed negative cooperativity of H4biopterin binding (h = 0.4).", "entity1": "hTH1", "entity2": "C", "span1": [57, 61], "span2": [12, 13]}, "weak_labels": [-1, -1, 0, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1554": {"label": 2, "data": {"text": "Treatment with diclofenac resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated caspase-3 after 6 hr, indicating that diclofenac may cause apoptosis of neuronal cells via activation of the caspase cascade.", "entity1": "caspase-3", "entity2": "diclofenac", "span1": [148, 157], "span2": [15, 25]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14929": {"label": 1, "data": {"text": "However, other steroids, including \u0394(5)-androstenediol, 5\u03b1-androstanediol and 27-hydroxycholesterol, which have a saturated A ring containing a 3\u03b2-hydroxyl and a C19 methyl group, also mediate physiological responses through binding to estrogen receptor-\u03b1 (ER\u03b1) and ER\u03b2.", "entity1": "ER\u03b2", "entity2": "methyl", "span1": [266, 269], "span2": [166, 172]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13932": {"label": 3, "data": {"text": "Both drugs at the tested doses (0.042-0.33 mug/kg) suppressed PTH mRNA expression and serum PTH effectively in the 5/6 NX rats, but paricalcitol was less potent in raising serum Ca than doxercalciferol.", "entity1": "PTH", "entity2": "paricalcitol", "span1": [62, 65], "span2": [132, 144]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9717": {"label": 3, "data": {"text": "Inhibition of AChE in the CSF after rivastigmine administration was significantly greater than after placebo for up to 8.4 hours after the dose and was maximal (40%) at 2.4 hours.", "entity1": "AChE", "entity2": "rivastigmine", "span1": [14, 18], "span2": [36, 48]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6853": {"label": 1, "data": {"text": "We studied several single nucleotide polymorphisms (SNP) in Hcy-regulating genes [methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C; methionine synthase (MS) A2756G; methionine synthase reductase (MTRR) A66G] in relation to total plasma Hcy levels, transplant coronary artery disease and thromboembolic episodes in 84 heart transplant patients, and we compared the incidence of these polymorphisms with those in a healthy adult controls.", "entity1": "A66G", "entity2": "Hcy", "span1": [214, 218], "span2": [60, 63]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11764": {"label": 1, "data": {"text": "This study also provides insight into the anticancer effects of VK2 and suggests that Bak may be a potential target of cancer therapy.", "entity1": "Bak", "entity2": "VK2", "span1": [86, 89], "span2": [64, 67]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13246": {"label": 3, "data": {"text": "Down-regulation of GRIP1 by glutamate was blocked by carbobenzoxyl-leucinyl-leucinyl-leucinal (MG132), a proteasome inhibitor and by expression of K48R-ubiquitin, a dominant negative form of ubiquitin.", "entity1": "proteasome", "entity2": "carbobenzoxyl-leucinyl-leucinyl-leucinal", "span1": [105, 115], "span2": [53, 93]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1721": {"label": 2, "data": {"text": "Ginsenosides Rb2, Rd and Rg1 significantly decreased norepinephrine and/or epinephrine-induced increase of IL-6 level in macrophage cell line (RAW 264.7).", "entity1": "IL-6", "entity2": "epinephrine", "span1": [107, 111], "span2": [75, 86]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11146": {"label": 8, "data": {"text": "Levodopa is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase (AADC) and catechol-O-methyltransferase (COMT).", "entity1": "aromatic-L-amino-acid decarboxylase", "entity2": "Levodopa", "span1": [70, 105], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15810": {"label": 3, "data": {"text": "Potency switch between CHK1 and MK2: Discovery of imidazo[1,2-a]pyrazine- and imidazo[1,2-c]pyrimidine-based kinase inhibitors.", "entity1": "MK2", "entity2": "imidazo[1,2-c]pyrimidine", "span1": [32, 35], "span2": [78, 102]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13576": {"label": 3, "data": {"text": "The next large phase III adjuvant trial for this subset of breast cancer is an international collaboration designed to evaluate the added or alternative benefit of an oral tyrosine kinase inhibitor targeting HER2/neu as well as the epidermal growth factor receptor (EGFR), lapatinib.", "entity1": "EGFR", "entity2": "lapatinib", "span1": [266, 270], "span2": [273, 282]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12888": {"label": 3, "data": {"text": "Sorafenib (BAY 43-9006) is a small-molecule inhibitor that has been shown to target members of multiple classes of tyrosine kinases that are known to be involved in tumor cell proliferation and tumor angiogenesis.", "entity1": "tyrosine kinases", "entity2": "BAY 43-9006", "span1": [115, 131], "span2": [11, 22]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8196": {"label": 2, "data": {"text": "Here, we show that oral administration of resveratrol, which leads to activation of an NAD(+)-dependent protein deacetylase SIRT1, suppresses cardiac hypertrophy and fibrosis and restores cardiac diastolic function in dystrophin-deficient mdx mice.", "entity1": "NAD(+)-dependent protein deacetylase SIRT1", "entity2": "resveratrol", "span1": [87, 129], "span2": [42, 53]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15702": {"label": 1, "data": {"text": "In an investigation into the participation of TRP channels and ASICs in CAT's antinociceptive mechanism, we used capsaicin (2.2\u03bcg/paw), cinnamaldehyde (10mmol/paw), menthol (1.2mmol/paw) and acidified saline (2% acetic acid, pH 1.98).", "entity1": "ASICs", "entity2": "cinnamaldehyde", "span1": [63, 68], "span2": [136, 150]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6581": {"label": 1, "data": {"text": "OBJECTIVE: Fondaparinux sodium is the first in a new class of synthetic factor Xa inhibitors that binds reversibly with high affinity to antithrombin III.", "entity1": "antithrombin III", "entity2": "Fondaparinux sodium", "span1": [137, 153], "span2": [11, 30]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5511": {"label": 4, "data": {"text": "In pigeons trained to discriminate 1.7 mg/kg dezocine from saline, a series of opioids with activity at the mu opioid receptor substituted completely for the dezocine stimulus with a rank order of potency similar to that obtained in other assays sensitive to the effects of mu agonists (i.e., fentanyl >[-]-cyclazocine >buprenorphine = butorphanol >l-methadone >nalbuphine >[-]-metazocine >morphine).", "entity1": "mu opioid receptor", "entity2": "morphine", "span1": [108, 126], "span2": [390, 398]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5024": {"label": 8, "data": {"text": "In four (10\u00a0%) patients the peak ACTH-stimulated cortisol values were lower than 18\u00a0\u03bcg/dL.", "entity1": "ACTH", "entity2": "cortisol", "span1": [33, 37], "span2": [49, 57]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11354": {"label": 8, "data": {"text": "Block of human NaV1.5 sodium channels by novel alpha-hydroxyphenylamide analogues of phenytoin.", "entity1": "human NaV1.5", "entity2": "sodium", "span1": [9, 21], "span2": [22, 28]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12039": {"label": 8, "data": {"text": "Compound I of the peroxidases is represented as EO, and oxidation of I- by EO is postulated to form enzyme-bound hypoiodite, represented in our scheme as [EOI]-.", "entity1": "EO", "entity2": "I-", "span1": [75, 77], "span2": [69, 71]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"84": {"label": 1, "data": {"text": "Cooperative homotropic interaction of L-noradrenaline with the catalytic site of phenylalanine 4-monooxygenase.", "entity1": "phenylalanine 4-monooxygenase", "entity2": "L-noradrenaline", "span1": [81, 110], "span2": [38, 53]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9745": {"label": 4, "data": {"text": "In vivo, agonist actions of yohimbine at 5-HT(1A) sites are revealed by WAY100,635-reversible induction of hypothermia in the rat.", "entity1": "5-HT(1A)", "entity2": "yohimbine", "span1": [41, 49], "span2": [28, 37]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5226": {"label": 2, "data": {"text": "Also, vinblastine enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaB\u03b1 (I\u03baB\u03b1) kinase, and inositol requiring enzyme 1\u03b1.", "entity1": "inositol requiring enzyme 1\u03b1", "entity2": "vinblastine", "span1": [295, 323], "span2": [6, 17]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6570": {"label": 3, "data": {"text": "Mutants Y751A, D950A, and F1004A had reduced sensitivity to milrinone (K(i) changed from 0.66 microM for the recombinant PDE3A to 7.5 to 156 microM for the mutants), and diminished sensitivity to cilostazol (K(i) of the mutants were 18- to 371-fold higher than that of the recombinant PDE3A).", "entity1": "PDE3A", "entity2": "milrinone", "span1": [121, 126], "span2": [60, 69]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13676": {"label": 1, "data": {"text": "Two imidazoquinoline molecules, imiquimod and gardiquimod, markedly activated both porcine TLR7 and TLR8 whereas only human TLR7, but not TLR8, was activated by the ligands.", "entity1": "porcine TLR7", "entity2": "imidazoquinoline", "span1": [83, 95], "span2": [4, 20]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"13224": {"label": 9, "data": {"text": "Here we report that glutamate stimulation caused a rapid reduction in protein levels of GRIP1, but not that of glutamate receptor (GluR) 1, GluR2 and protein interacting with C kinase 1 (PICK1) in rat primary cortical neuron cultures.", "entity1": "PICK1", "entity2": "glutamate", "span1": [187, 192], "span2": [20, 29]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, 2, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"2352": {"label": 4, "data": {"text": "Effect of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist, on motor performance in mice.", "entity1": "MT1/MT2 receptor", "entity2": "ramelteon", "span1": [43, 59], "span2": [10, 19]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4971": {"label": 3, "data": {"text": "One exception is tranexamic acid (TXA), which, as a lysine mimetic, inhibits binding of plasminogen to fibrin.", "entity1": "fibrin", "entity2": "lysine", "span1": [103, 109], "span2": [52, 58]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5165": {"label": 8, "data": {"text": "At a substrate concentration of 20\u2009\u00b5M, the most active HFC glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300\u2009\u00b5M UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.", "entity1": "UGT1A6", "entity2": "HFC", "span1": [110, 116], "span2": [55, 58]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, 8, -1, -1, -1]},
	"152": {"label": 1, "data": {"text": "The interaction of naloxone estrone azine (N-EH) with various opioid receptor types was studied in vitro.", "entity1": "opioid receptor", "entity2": "N-EH", "span1": [62, 77], "span2": [43, 47]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2704": {"label": 3, "data": {"text": "Sitagliptin, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide.", "entity1": "DPP-4", "entity2": "Sitagliptin", "span1": [104, 109], "span2": [0, 11]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"3174": {"label": 4, "data": {"text": "Terbutaline (Bricanyl) and its prodrug Bambuterol (Bambec) are highly potent beta(2)-adrenoceptor agonists often used in asthma patients.", "entity1": "beta(2)-adrenoceptor", "entity2": "Bricanyl", "span1": [77, 97], "span2": [13, 21]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2343": {"label": 1, "data": {"text": "We conclude that lutein and EPA interact through the PPARgamma and RXR pathways to modulate iNOS mRNA.", "entity1": "RXR", "entity2": "EPA", "span1": [67, 70], "span2": [28, 31]}, "weak_labels": [-1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8304": {"label": 1, "data": {"text": "Actin binding was unchanged by presence of nucleotide.", "entity1": "Actin", "entity2": "nucleotide", "span1": [0, 5], "span2": [43, 53]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15068": {"label": 9, "data": {"text": "Our in vitro studies showed that cyclic adenosine 3',5'-monophosphate (cAMP) accumulation was not a primary cause of the ritodrine-induced SAA increase.", "entity1": "SAA", "entity2": "cAMP", "span1": [139, 142], "span2": [71, 75]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"8292": {"label": 2, "data": {"text": "LY294002, a specific PI3K/AKT inhibitor, selectively activated the p38 MAPK kinase pathway and enhanced c-Jun phosphorylation, but did not activate JNK.", "entity1": "p38", "entity2": "LY294002", "span1": [67, 70], "span2": [0, 8]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"801": {"label": 2, "data": {"text": "Science, 9(266) (1994) 1709-1713) greatly attenuates the lithium-induced potentiation of GluR3.", "entity1": "GluR3", "entity2": "lithium", "span1": [89, 94], "span2": [57, 64]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10824": {"label": 3, "data": {"text": "Increased immunohistochemical labeling of HIF-1alpha, VEGF, and BNP in the ventricular myocardium was observed in the banding group and carvedilol again normalized the labeling.", "entity1": "HIF-1alpha", "entity2": "carvedilol", "span1": [42, 52], "span2": [136, 146]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3728": {"label": 3, "data": {"text": "The present results indicated that N-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways.", "entity1": "mTOR", "entity2": "N", "span1": [244, 248], "span2": [35, 36]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"10433": {"label": 0, "data": {"text": "The phosphate group of PLP is surrounded by a characteristic G-rich sequence ((168)GGGGL(172)) and forms hydrogen bonds with the amide groups of those amino acid residues, suggesting that the phosphate group can be protonated.", "entity1": "G-rich sequence", "entity2": "PLP", "span1": [61, 76], "span2": [23, 26]}, "weak_labels": [0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2044": {"label": 3, "data": {"text": "Docetaxel is a semisynthetic taxane that inhibit tumor growth by induction of microtubule stabilization and promotion of bcl-2 inactivation, which induce apoptosis.", "entity1": "bcl-2", "entity2": "taxane", "span1": [121, 126], "span2": [29, 35]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14959": {"label": 2, "data": {"text": "Bile acids are signaling molecules that activate nuclear receptors, such as farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, and vitamin D receptor, and play a critical role in the regulation of lipid, glucose, energy, and drug metabolism.", "entity1": "pregnane X receptor", "entity2": "Bile acids", "span1": [98, 117], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5548": {"label": 2, "data": {"text": "This study investigates the involvement of alpha(2)-adrenergic receptors (AR) in mouse brain induced by a low dose of methamphetamine (METH, 2 mg/kg).", "entity1": "AR", "entity2": "methamphetamine", "span1": [74, 76], "span2": [118, 133]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3672": {"label": 3, "data": {"text": "Moreover, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that artemisinic acid regulated melanogenesis by inhibiting cholesterol synthesis through downregulation of the hydroxymethylglutaryl CoA (HMG CoA) reductase gene, which was mediated through reduced expression of the CCAAT/enhancer-binding protein (C/EBP) \u03b1 gene.", "entity1": "hydroxymethylglutaryl CoA (HMG CoA) reductase", "entity2": "artemisinic acid", "span1": [223, 268], "span2": [116, 132]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, 3, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2811": {"label": 3, "data": {"text": "Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS.", "entity1": "E-selectin", "entity2": "1400W", "span1": [186, 196], "span2": [119, 124]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11028": {"label": 3, "data": {"text": "Further characterization showed that sorafenib suppresses both wild-type and V599E mutant B-Raf activity in vitro.", "entity1": "B-Raf", "entity2": "sorafenib", "span1": [90, 95], "span2": [37, 46]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2744": {"label": 3, "data": {"text": "Preclinical pharmacokinetics and in vitro metabolism of dasatinib (BMS-354825): a potent oral multi-targeted kinase inhibitor against SRC and BCR-ABL.", "entity1": "SRC", "entity2": "BMS-354825", "span1": [134, 137], "span2": [67, 77]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15776": {"label": 4, "data": {"text": "Agonistic activity of ICI 182 780 on activation of GSK 3\u03b2/AKT pathway in the rat uterus during the estrous cycle.", "entity1": "GSK 3\u03b2", "entity2": "ICI 182 780", "span1": [51, 57], "span2": [22, 33]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"766": {"label": 0, "data": {"text": "The inhibitor binds at the base of the active site gorge of TcAChE, interacting with both the choline-binding site (Trp-84) and the acyl-binding pocket (Phe-288, Phe-290).", "entity1": "acyl-binding pocket", "entity2": "Phe", "span1": [132, 151], "span2": [153, 156]}, "weak_labels": [-1, -1, -1, 1, 1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2660": {"label": 3, "data": {"text": "A broad-spectrum phosphodiesterase (PDE) inhibitor (1,3-isobutyl-1-methylxanthine, 300 microM, n=6) and an ecto-phosphodiesterase inhibitor (1,3-dipropyl-8-p-sulfophenylxanthine, 1 mM, n=6) significantly attenuated cAMP-induced AMP secretion by 60 and 74%, respectively.", "entity1": "PDE", "entity2": "1,3-isobutyl-1-methylxanthine", "span1": [36, 39], "span2": [52, 81]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14543": {"label": 3, "data": {"text": "Protein tyrosine phosphatase 1B inhibitory effect by dammarane-type triterpenes from hydrolyzate of total Gynostemma pentaphyllum saponins.", "entity1": "Protein tyrosine phosphatase 1B", "entity2": "dammarane", "span1": [0, 31], "span2": [53, 62]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"7016": {"label": 3, "data": {"text": "Sorafenib has the added advantage of inhibiting multiple different Raf isoforms, which enables it to target TGF-alpha/EGFR signaling and may also enhance its inhibition of VEGFR and PDGFR-beta.", "entity1": "PDGFR-beta", "entity2": "Sorafenib", "span1": [182, 192], "span2": [0, 9]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4288": {"label": 1, "data": {"text": "Flavonoids such as green tea catechins and quercetin glycosides have been shown to modulate the function of some OATPs.", "entity1": "OATPs", "entity2": "catechins", "span1": [113, 118], "span2": [29, 38]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9507": {"label": 1, "data": {"text": "Saturation and competition studies in the presence or absence of the histamine H1 receptor antagonist, levocabastine, revealed that [3H]SR 142948A bound with similar affinities to both the levocabastine-insensitive neurotensin NT1 receptors (20% of the total binding population) and the recently cloned levocabastine-sensitive neurotensin NT2 receptors (80% of the receptors) (Kd = 6.8 and 4.8 nM, respectively).", "entity1": "neurotensin NT1 receptors", "entity2": "[3H]SR 142948A", "span1": [215, 240], "span2": [132, 146]}, "weak_labels": [-1, -1, -1, 1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"911": {"label": 1, "data": {"text": "Betaxolol inhibited specific [(3)H]-batrachotoxinin-A 20-alpha-benzoate ([(3)H]-BTX-B) binding to neurotoxin site 2 in a concentration-dependent manner with an IC(50) value of 9.8 microM.", "entity1": "neurotoxin site 2", "entity2": "[(3)H]-batrachotoxinin-A 20-alpha-benzoate", "span1": [98, 115], "span2": [29, 71]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9628": {"label": 2, "data": {"text": "The ATP-sensitive potassium (KATP) channels in pancreatic beta cells are critical in the regulation of glucose-induced insulin secretion.", "entity1": "insulin", "entity2": "glucose", "span1": [119, 126], "span2": [103, 110]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8237": {"label": 5, "data": {"text": "PNU-282987 on the other hand displayed an increase in anxiety-like behavior at a higher dose (10\u00a0mg/kg) that was significantly reduced by the serotonin 5-HT1a receptor antagonist WAY-100135.", "entity1": "serotonin 5-HT1a receptor", "entity2": "WAY-100135", "span1": [142, 167], "span2": [179, 189]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"15061": {"label": 1, "data": {"text": "Similarly, intraperitoneal administration of \u03b1-santalol (100mg/kg BW) and sandalwood oil (1g/kg BW) for two weeks modulated parameters such as serum aminotransferases, alkaline phosphatase, bilirubin, superoxide dismutase, catalase, free sulfhydryl, protein carbonyl, nitric oxide, liver lipid peroxide contents, and antioxidant capacity in d-galactose mediated oxidative stress induced mice.", "entity1": "aminotransferases", "entity2": "\u03b1-santalol", "span1": [149, 166], "span2": [45, 55]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, 9]},
	"8954": {"label": 3, "data": {"text": "The 3 beta-hydroxysteroid substrate, pregnenolone, protects isomerase as well as dehydrogenase from inactivation by FSA.", "entity1": "dehydrogenase", "entity2": "FSA", "span1": [81, 94], "span2": [116, 119]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"3972": {"label": 1, "data": {"text": "To control for possible interactions between the expression of the estrogen receptor genes and other learning-related steroid receptors, androgen receptors (AR), corticosterone-binding glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) were also measured.", "entity1": "mineralocorticoid receptors", "entity2": "corticosterone", "span1": [219, 246], "span2": [162, 176]}, "weak_labels": [-1, -1, -1, 1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1709": {"label": 8, "data": {"text": "The choroid plexus uptake of [(3)H]cefadroxil was studied in peptide transporter 2 (PEPT2) wild-type and null mice as a function of temperature, transport inhibitors, pH, and saturability.", "entity1": "PEPT2", "entity2": "[(3)H]cefadroxil", "span1": [84, 89], "span2": [29, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1]},
	"1696": {"label": 3, "data": {"text": "BACKGROUND: Rivastigmine is a carbamate drug designed to inhibit both acetylcholinesterase and butyrylcholinesterase by reversibly covalently bonding to these enzymes.", "entity1": "butyrylcholinesterase", "entity2": "Rivastigmine", "span1": [95, 116], "span2": [12, 24]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3379": {"label": 5, "data": {"text": "Ca(v)1.3 channels were less sensitive to pentobarbital inhibition than Ca(v)1.2 channels, similar to dihydropyridine (DHP) L-VGCC antagonists.", "entity1": "L-VGCC", "entity2": "DHP", "span1": [123, 129], "span2": [118, 121]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1659": {"label": 5, "data": {"text": "The potent histamine H(1)-receptor antagonist cetirizine (Zyrtec) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and dextrocetirizine.", "entity1": "histamine H(1)-receptor", "entity2": "Xyzal", "span1": [11, 34], "span2": [140, 145]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6746": {"label": 3, "data": {"text": "Although highly homologous to other class III RTKs, Flt3 is resistant to the phenylaminopyrimidine STI571 (Gleevec, Imatinib), a potent inhibitor of other RTKs in the family, such as the PDGFbeta-receptor or c-Kit.", "entity1": "PDGFbeta-receptor", "entity2": "STI571", "span1": [187, 204], "span2": [99, 105]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12948": {"label": 5, "data": {"text": "However, several promising nonpeptide, vasopressin receptor antagonists have been described; these agents are VPA-985 (lixivaptan), YM-087 (conivaptan), OPC-41061 (tolvaptan), and SR-121463.", "entity1": "vasopressin receptor", "entity2": "OPC-41061", "span1": [39, 59], "span2": [153, 162]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 5, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8382": {"label": 3, "data": {"text": "The obtained results showed that Cd increased lipid peroxidation and abnormal sperm count and decreased plasma testosterone, lactate dehydrogenase, acid phosphatase, alkaline phosphatase and testicular steroidogenic enzymes: 3\u03b2-hydroxysteroid dehydrogenase (HSD), 17\u03b2-HSD activities as well as epididymal sperm counts and motility, while RUT and Se treatment reversed this change to control values.", "entity1": "alkaline phosphatase", "entity2": "Cd", "span1": [166, 186], "span2": [33, 35]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12594": {"label": 1, "data": {"text": "Coexpression of the flip and flop splice variants of GluR-A, in the absence of GluR-B, revealed that heteromeric AMPA receptors with intermediate sensitivity to cyclothiazide, similar to responses observed for the combinations GluR-AoBi or GluR-AiBo, could be generated independently of the presence of the GluR-B subunit.", "entity1": "AMPA receptors", "entity2": "cyclothiazide", "span1": [113, 127], "span2": [161, 174]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2939": {"label": 1, "data": {"text": "Vardenafil has higher affinity to phosphodiesterase-5 (PDE5) than sildenafil and lower administered dosage for the treatment of erectile dysfunction.", "entity1": "PDE5", "entity2": "Vardenafil", "span1": [55, 59], "span2": [0, 10]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8886": {"label": 3, "data": {"text": "By \"working upwards\" from mTOR, we observed that TCDD inhibited endogenous and IGF-I-induced AKT and ERK activation by interfering with tyrosine phosphorylation of insulin receptor substrate 1.", "entity1": "ERK", "entity2": "TCDD", "span1": [101, 104], "span2": [49, 53]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"14258": {"label": 8, "data": {"text": "Here, we show that siRNA-mediated knockdown of SSAT2 in HEPG2 cells and in primary hepatocytes from the SSAT1-deficient or wild-type mice reduced the metabolism of TETA to MAT.", "entity1": "SSAT2", "entity2": "TETA", "span1": [47, 52], "span2": [164, 168]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"8424": {"label": 8, "data": {"text": "Furthermore, knockdown of OPN enhanced cell death caused by other drugs, including paclitaxel, doxorubicin, actinomycin-D, and rapamycin, which are also P-gp substrates.", "entity1": "P-gp", "entity2": "actinomycin-D", "span1": [153, 157], "span2": [108, 121]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"4628": {"label": 4, "data": {"text": "The results suggested that both the EtOAc extract and berberine were able to activate PPAR\u03b1/\u03b2/\u03b3, and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.", "entity1": "PPAR\u03b1/\u03b2/\u03b3", "entity2": "berberine", "span1": [86, 95], "span2": [169, 178]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9016": {"label": 4, "data": {"text": "The limitation of SRF by diazepam was not prevented by inverse or partial agonists at the BDZ receptor, including Ro 15-1788 and the beta CCs.", "entity1": "BDZ receptor", "entity2": "beta CCs", "span1": [90, 102], "span2": [133, 141]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"5565": {"label": 2, "data": {"text": "Treatment of cells with BCNU to inhibit glutathione reductase (GR) enhanced the CpG-induced intracellular oxidation and decreased the GSH/GSSG, with increased activation of NF-kappaB and a doubling in the CpG-induced production of IL-6 and TNF-alpha.", "entity1": "TNF-alpha", "entity2": "GSSG", "span1": [240, 249], "span2": [138, 142]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, 2, 2, -1, -1, -1, 3, 3, 3, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"5840": {"label": 3, "data": {"text": "Terbinafine (Lamisil) has primarily fungicidal action against many fungi as a result of its specific mechanism of squalene epoxidase inhibition.", "entity1": "squalene epoxidase", "entity2": "Lamisil", "span1": [114, 132], "span2": [13, 20]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"14368": {"label": 2, "data": {"text": "Several effects of polyphenols are useful in this scenario, including a reduction in the activities of cytokines and modulation of cellular metabolism through histone deacetylase inhibitors, AMPK activators, calorie-restriction mimetics or epigenetic regulators.", "entity1": "AMPK", "entity2": "polyphenols", "span1": [191, 195], "span2": [19, 30]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, 3, -1, -1, -1, 6, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11606": {"label": 8, "data": {"text": "Hydrogen sulphide (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS).", "entity1": "CBS", "entity2": "L-cysteine", "span1": [140, 143], "span2": [46, 56]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"12639": {"label": 1, "data": {"text": "Although electrophysiological studies provide clues to the complex control of KATP channels by ATP, MgADP, and pharmacological agents, the molecular mechanism of KATP-channel regulation remains unclear.", "entity1": "KATP channels", "entity2": "MgADP", "span1": [78, 91], "span2": [100, 105]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"13352": {"label": 1, "data": {"text": "INTRODUCTION: Medroxyprogesterone acetate (MPA) induces estrogen receptor (ER)-positive and progesterone receptor (PR)-positive ductal invasive mammary carcinomas in BALB/c mice.", "entity1": "progesterone receptor", "entity2": "MPA", "span1": [92, 113], "span2": [43, 46]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6709": {"label": 3, "data": {"text": "The results demonstrated that tranylcypromine is a competitive inhibitor of CYP2C19 (Ki = 32 microM) and CYP2D6 (Ki = 367 microM) and a noncompetitive inhibitor of CYP2C9 (Ki = 56 microM).", "entity1": "CYP2D6", "entity2": "tranylcypromine", "span1": [105, 111], "span2": [30, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1978": {"label": 1, "data": {"text": "Thus far, PHA1 has been attributed to mutations affecting the mineralocorticoid receptor or any of the three subunits assembling the amilorideamiloride-sensitive epithelial sodium channel (ENaC).", "entity1": "amiloride-sensitive epithelial sodium channel", "entity2": "amiloride", "span1": [142, 187], "span2": [133, 142]}, "weak_labels": [-1, -1, 0, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11967": {"label": 8, "data": {"text": "PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase \u03b2 type I (pip5k1\u03b2), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2].", "entity1": "phosphatidylinositol 4-phosphate 5-kinase \u03b2 type I", "entity2": "phosphatidylinositol 4-phosphate", "span1": [16, 66], "span2": [159, 191]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"5130": {"label": 3, "data": {"text": "In this study, we found that 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone (5HHMF) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of inducible NO synthase (iNOS) in BV2 microglia.", "entity1": "iNOS", "entity2": "5HHMF", "span1": [230, 234], "span2": [72, 77]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, 2, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"301": {"label": 2, "data": {"text": "It is concluded that D-1997 contracts the canine basilar artery by stimulating 5-HT1-like receptors unrelated to either the 5-HT1A or 5-HT1B receptor subtypes.", "entity1": "5-HT1-like receptors", "entity2": "D-1997", "span1": [79, 99], "span2": [21, 27]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9298": {"label": 8, "data": {"text": "We conclude that expression of GLUT2 is required for efficient killing of neuroendocrine cells by STZ, and this effect is related to specific recognition of the drug as a transported substrate by GLUT2 but not GLUT1.", "entity1": "GLUT2", "entity2": "STZ", "span1": [196, 201], "span2": [98, 101]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, 8, -1, -1, -1, 9]},
	"12707": {"label": 1, "data": {"text": "However, when coapplied with 10 micro m GABA, ivermectin potentiated the GABA-evoked current of the GAB-1/HG1A receptor, but attenuated the GABA response of the GAB-1/HG1E receptor.", "entity1": "GAB-1", "entity2": "GABA", "span1": [161, 166], "span2": [140, 144]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4528": {"label": 2, "data": {"text": "Our results showed that low dose BPA and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of Oct4 and Nanog proteins, while only BPA could downregulate the expression of E-cadherin protein.", "entity1": "Oct4", "entity2": "BPA", "span1": [130, 134], "span2": [33, 36]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 2, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"87": {"label": 3, "data": {"text": "Catecholamines (adrenaline, noradrenaline and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase (phenylalanine hydroxylase, EC 1.14.16.1).", "entity1": "phenylalanine hydroxylase", "entity2": "adrenaline", "span1": [112, 137], "span2": [16, 26]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1864": {"label": 3, "data": {"text": "Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase (DGAT).", "entity1": "DGAT", "entity2": "kushenol H", "span1": [253, 257], "span2": [89, 99]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2674": {"label": 8, "data": {"text": "In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to AMP by ecto-phosphodiesterase, and metabolism of AMP to adenosine by ecto-5'-nucleotidase.", "entity1": "phosphodiesterase", "entity2": "AMP", "span1": [101, 118], "span2": [89, 92]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1]},
	"6184": {"label": 2, "data": {"text": "Additional neuroendocrine experiments in a parallel group of rats revealed a dose-related increase in plasma prolactin and ACTH levels after i.v. mCPP, pointing to a general state of arousal in these mCPP-treated animals.", "entity1": "plasma prolactin", "entity2": "mCPP", "span1": [102, 118], "span2": [146, 150]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2722": {"label": 1, "data": {"text": "Other QTc interval-prolonging/arrhythmic drugs that also bind to HERG provided an analogy for cisapride causing QTc interval prolongation/arrhythmia via this mechanism.", "entity1": "HERG", "entity2": "cisapride", "span1": [65, 69], "span2": [94, 103]}, "weak_labels": [-1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1688": {"label": 3, "data": {"text": "Moreover, recent in vitro studies suggest that memantine abrogates beta-amyloid (Abeta) toxicity and possibly inhibits Abeta production.", "entity1": "Abeta", "entity2": "memantine", "span1": [81, 86], "span2": [47, 56]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1]},
	"5195": {"label": 2, "data": {"text": "High glucose (HG) induces apoptosis of podocytes, inhibits AMPK activation, inactivates tuberin and activates mTOR.", "entity1": "mTOR", "entity2": "glucose", "span1": [110, 114], "span2": [5, 12]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2911": {"label": 8, "data": {"text": "Coagulation-induced thromboxane B(2) and lipopolysaccharide-induced prostaglandin E(2) were measured ex vivo and in vitro in human whole blood as indices of COX-1 and COX-2 activity.", "entity1": "COX-1", "entity2": "thromboxane B(2)", "span1": [157, 162], "span2": [20, 36]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"9719": {"label": 3, "data": {"text": "BuChE activity in CSF was significantly lower after rivastigmine than after placebo for up to 3.6 hours after dosing, but this difference was not sustained.", "entity1": "BuChE", "entity2": "rivastigmine", "span1": [0, 5], "span2": [52, 64]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"1852": {"label": 3, "data": {"text": "Carbonic anhydrase inhibitors: aromatic and heterocyclic sulfonamides incorporating adamantyl moieties with strong anticonvulsant activity.", "entity1": "Carbonic anhydrase", "entity2": "aromatic and heterocyclic sulfonamides", "span1": [0, 18], "span2": [31, 69]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11953": {"label": 8, "data": {"text": "UGT1A6 exhibited a significantly higher Vmax and Km values toward both HFC and UDP-glucuronic acid than the other UGTs.", "entity1": "UGTs", "entity2": "UDP", "span1": [114, 118], "span2": [79, 82]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11474": {"label": 1, "data": {"text": "Melatonin and N-acetyl-5-hydroxytryptamine (N-acetyl-5-HT), a ligand of MT3 biding site, also had no impairment on the performance, per se.", "entity1": "MT3", "entity2": "N-acetyl-5-HT", "span1": [72, 75], "span2": [44, 57]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"4417": {"label": 3, "data": {"text": "Notably, 17-HDHA treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression and improved glucose tolerance parallel to insulin sensitivity in obese mice.", "entity1": "cytokines", "entity2": "17-HDHA", "span1": [77, 86], "span2": [9, 16]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 9]},
	"19": {"label": 3, "data": {"text": "Preincubation for 30 minutes with iloprost, ciprostene, and carbacyclin led to a dose-dependent inhibition of tissue factor expression induced by all three challenging agents.", "entity1": "tissue factor", "entity2": "carbacyclin", "span1": [110, 123], "span2": [60, 71]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3022": {"label": 3, "data": {"text": "Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2.", "entity1": "histone deacetylase", "entity2": "Statins", "span1": [43, 62], "span2": [0, 7]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6520": {"label": 3, "data": {"text": "We tested the new orally active nonpeptidic renin inhibitor SPP100 (Aliskiren, an octanamide with a 50% inhibitory concentration [IC50] in the low nanomolar range) in 18 healthy volunteers on a constant 100 mmol/d sodium diet using a double-blind, 3-way crossover protocol.", "entity1": "renin", "entity2": "octanamide", "span1": [44, 49], "span2": [82, 92]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3406": {"label": 3, "data": {"text": "Pseudoephedrine inhibits T-cell activation by targeting NF-kappaB, NFAT and AP-1 signaling pathways.", "entity1": "NFAT", "entity2": "Pseudoephedrine", "span1": [67, 71], "span2": [0, 15]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"3803": {"label": 3, "data": {"text": "These findings demonstrate that cinnamon polyphenols can exert the hypoglycemic and hypolipidemic effects through the mechanisms that may be associated with repairing pancreatic beta cells in diabetic mice and improving its anti-oxidative capacity, as well as attenuating cytotoxicity via inhibition of iNOS, NF-\u03baB activation.", "entity1": "iNOS", "entity2": "polyphenols", "span1": [303, 307], "span2": [41, 52]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"2985": {"label": 1, "data": {"text": "Catalytic-site affinities for cGMP, vardenafil, sildenafil, tadalafil, or 3-isobutyl-1-methylxanthine (IBMX) were respectively weakened 14-, 123-, 30-, 51-, and 43-fold for Y612A; 63-, 511-, 43-, 95- and 61-fold for Q817A; and 59-, 448-, 71-, 137-, and 93-fold for F820A.", "entity1": "Y612A", "entity2": "vardenafil", "span1": [173, 178], "span2": [36, 46]}, "weak_labels": [-1, -1, -1, -1, -1, 1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6404": {"label": 3, "data": {"text": "In a physiological K(+) gradient, TWIK-2 is half inhibited by 0.1 mm Ba(2+), quinine, and quinidine.", "entity1": "TWIK-2", "entity2": "Ba(2+)", "span1": [34, 40], "span2": [69, 75]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1508": {"label": 4, "data": {"text": "OBJECTIVE: Preclinical evaluation of DRF 2655, a peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent.", "entity1": "peroxisome proliferator-activated receptor alpha", "entity2": "DRF 2655", "span1": [49, 97], "span2": [37, 45]}, "weak_labels": [-1, -1, -1, -1, -1, -1, 2, -1, -1, -1, -1, -1, -1, -1, -1, 4, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"11681": {"label": 1, "data": {"text": "We postulate that vescalagin is an active component in PWFE that may alleviate the insulin resistance in mouse hepatocytes.", "entity1": "insulin", "entity2": "vescalagin", "span1": [83, 90], "span2": [18, 28]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"1196": {"label": 8, "data": {"text": "Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B.", "entity1": "leucine aminopeptidase", "entity2": "L-leucine", "span1": [231, 253], "span2": [217, 226]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1, -1, -1]},
	"1706": {"label": 8, "data": {"text": "At normal pH (7.4) and temperature (37 degrees C), the uptake of 1 microM cefadroxil was reduced by 83% in PEPT2(-/-) mice as compared with PEPT2(+/+) mice (p < 0.001).", "entity1": "PEPT2", "entity2": "cefadroxil", "span1": [107, 112], "span2": [74, 84]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 3, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]},
	"6383": {"label": 8, "data": {"text": "Ornithine decarboxylase (ODC) catalyses the first step in the synthesis of the polyamines putrescine, spermidine and spermine.", "entity1": "Ornithine decarboxylase", "entity2": "spermidine", "span1": [0, 23], "span2": [102, 112]}, "weak_labels": [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, 8, -1, -1, -1]}
}