zaprinast [Ligand Id: 2919] activity data from GtoPdb and ChEMBL

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ChEMBL ligand: CHEMBL28079 (M&B 22948, NSC-757885, Zaprinast)
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  • phosphodiesterase 10A/Phosphodiesterase 10A in Human [ChEMBL: CHEMBL4409] [GtoPdb: 1310] [UniProtKB: Q9Y233]
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  • phosphodiesterase 11A/Phosphodiesterase 11A in Human [ChEMBL: CHEMBL2717] [GtoPdb: 1311] [UniProtKB: Q9HCR9]
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  • phosphodiesterase 1C/Phosphodiesterase 1C in Human [ChEMBL: CHEMBL4619] [GtoPdb: 1296] [UniProtKB: Q14123]
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  • phosphodiesterase 2A/Phosphodiesterase 2A in Human [ChEMBL: CHEMBL2652] [GtoPdb: 1297] [UniProtKB: O00408]
  • phosphodiesterase 2A/Phosphodiesterase 2A in Rat [ChEMBL: CHEMBL4650] [GtoPdb: 1297] [UniProtKB: Q01062]
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  • phosphodiesterase 4A/Phosphodiesterase 4A in Human [ChEMBL: CHEMBL254] [GtoPdb: 1300] [UniProtKB: P27815]
  • Phosphodiesterase 4A in Pig [ChEMBL: CHEMBL3333] [UniProtKB: O77823]
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  • phosphodiesterase 4B/Phosphodiesterase 4B in Human [ChEMBL: CHEMBL275] [GtoPdb: 1301] [UniProtKB: Q07343]
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  • phosphodiesterase 4D/Phosphodiesterase 4D in Human [ChEMBL: CHEMBL288] [GtoPdb: 1303] [UniProtKB: Q08499]
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  • phosphodiesterase 9A/Phosphodiesterase 9A in Human [ChEMBL: CHEMBL3535] [GtoPdb: 1309] [UniProtKB: O76083]
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  • mitochondrial pyruvate carrier 2 in Human [GtoPdb: 3023] [UniProtKB: O95563]
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DB Assay description Assay Type Standard value Standard parameter Original value Original units Original parameter Reference
GPR35/G-protein coupled receptor 35 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1293267] [GtoPdb: 102] [UniProtKB: Q9HC97]
ChEMBL Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis B 6.4 pKi 401 nM Ki J Med Chem (2013) 56: 7084-7099 [PMID:23888932]
ChEMBL Antagonist activity at GPR35 in human HT-29 cells assessed as inhibition of zaprinast-induced DMR by dynamic mass redistribution assay F 4.98 pIC50 10500 nM IC50 J Med Chem (2011) 54: 7385-7396 [PMID:21950657]
ChEMBL Agonist activity at GPR35 in human HT-29 cells assessed as desensitization of 1 uM zaprinast-induced DMR after 1 hr by dynamic mass redistribution assay F 5.91 pIC50 1220 nM IC50 J Med Chem (2011) 54: 7385-7396 [PMID:21950657]
ChEMBL Desensitization of GPR35 receptor in human HT-29 cells assessed as inhibition of zaprinast-induced dynamic mass redistribution after 10 mins B 5.91 pIC50 1220 nM IC50 ACS Med Chem Lett (2012) 3: 165-169 [PMID:24900447]
ChEMBL Agonist activity at human GPR35 receptor expressed in CHO-K1 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay F 7.32 pIC50 48.15 nM IC50 J Med Chem (2021) 64: 2634-2647 [PMID:33630609]
ChEMBL Agonist activity at GPR35 in human U20S cells expressing beta-lactamase and Gal4-VP16 transcription factor assessed as beta arrestin translocation after 5 hrs by Tango assay F 5.21 pEC50 6200 nM EC50 Bioorg Med Chem Lett (2012) 22: 4148-4152 [PMID:22572579]
ChEMBL Agonist activity at GPR35 receptor in human U2OS cells coexpressing Gal4-VP16-TEV assessed as beta arrestin translocation after 5 hrs by beta lactamase reporter gene assay F 5.21 pEC50 6100 nM EC50 ACS Med Chem Lett (2012) 3: 165-169 [PMID:24900447]
ChEMBL Agonist activity at human GPR35 expressed in U2OS cells coexpressing Gal4-VP16/beta-arrestin fusion protein after 5 hrs by tango beta-arrestin translocation reporter gene assay F 5.28 pEC50 5300 nM EC50 ACS Med Chem Lett (2012) 3: 550-554 [PMID:24900508]
ChEMBL Agonist activity at human GPR35 expressed in CHO-K1 cells after 90 mins by beta-arrestin 2 recruitment assay B 5.38 pEC50 4200 nM EC50 J Med Chem (2017) 60: 362-372 [PMID:27976894]
ChEMBL Agonist activity at GPR35 in human U20S cells expressing beta-lactamase and GPR35-GA14-VP16 transcription factor fusion protein assessed as transcriptional activation after 5 hrs by tango beta-arrestin translocation reporter assay F 5.38 pEC50 4200 nM EC50 J Med Chem (2011) 54: 7385-7396 [PMID:21950657]
ChEMBL Agonist activity at TEV protease cleavage site linked GAL4-VP16-fused GPR35 in human Tango GPR35-bla U2OS cells assessed as induction of TEV protease-tagged beta-arrestin recruitment incubated for 5 hrs by beta-lactamase reporter gene assay B 5.45 pEC50 3520 nM EC50 J Med Chem (2017) 60: 362-372 [PMID:27976894]
ChEMBL Agonist activity at GPR35 in human U2OS cells assessed as induction of beta-arrestin translocation after 5 hrs by beta-lactamase reporter gene assay B 5.49 pEC50 3250 nM EC50 Medchemcomm (2012) 3: 1270-1274
ChEMBL Agonist activity at human GPR35b expressed in CHO cells assessed as induction of beta-arrestin recruitment after 90 mins by beta-galactosidase reporter gene assay B 5.65 pEC50 2240 nM EC50 J Med Chem (2013) 56: 5182-5197 [PMID:23713606]
ChEMBL Agonist activity at human GPR35 assessed as induction of beta-arrestin recruitment F 5.7 pEC50 2000 nM EC50 ACS Med Chem Lett (2018) 9: 422-427 [PMID:29795753]
ChEMBL Agonist activity at human GPR35 expressed in CHO cells assessed as induction of beta-arrestin recruitment after 90 mins by beta-galactosidase reporter gene assay B 5.71 pEC50 1960 nM EC50 J Med Chem (2013) 56: 5182-5197 [PMID:23713606]
GtoPdb - - 6.1 pEC50 - - - FEBS Lett (2006) 580: 5003-8 [PMID:16934253]
ChEMBL Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as dynamic mass redistribution response by DMR assay F 6.47 pEC50 340 nM EC50 J Med Chem (2021) 64: 2634-2647 [PMID:33630609]
ChEMBL Agonist activity at GPR35 in human HT-29 cells by DMR assay B 6.47 pEC50 340 nM EC50 J Med Chem (2017) 60: 362-372 [PMID:27976894]
ChEMBL Agonist activity at GPR35 in human HT-29 cells by dynamic mass redistribution assay F 6.8 pEC50 160 nM EC50 Bioorg Med Chem Lett (2012) 22: 4148-4152 [PMID:22572579]
ChEMBL Agonist activity at human GPR35 expressed in CHO-K1 cells by DMR assay B 6.8 pEC50 160 nM EC50 J Med Chem (2017) 60: 362-372 [PMID:27976894]
ChEMBL Agonist activity at GPR35 in human HT-29 cells after 1 hr by dynamic mass redistribution assay F 6.8 pEC50 160 nM EC50 J Med Chem (2011) 54: 7385-7396 [PMID:21950657]
ChEMBL Agonist activity at GPR35 receptor in human HT-29 cells after 10 mins by dynamic mass redistribution assay F 6.8 pEC50 160 nM EC50 ACS Med Chem Lett (2012) 3: 165-169 [PMID:24900447]
ChEMBL Agonist activity at GPR35 in human HT-29 cells measured after 10 mins by dynamic mass redistribution assay F 6.85 pEC50 140 nM EC50 ACS Med Chem Lett (2012) 3: 550-554 [PMID:24900508]
ChEMBL Agonist activity at human GPR35 by Ca+2 release assay B 6.89 pEC50 130 nM EC50 J Med Chem (2013) 56: 7084-7099 [PMID:23888932]
ChEMBL Agonist activity at GPR35 in human HT-29 cells assessed as induction of whole cell dynamic mass redistribution after 50 mins by resonant waveguide grating biosensor analysis B 6.96 pEC50 110 nM EC50 Medchemcomm (2012) 3: 1270-1274
ChEMBL Agonist activity at human GPR35 receptor expressed in CHO-K1 cells assessed as dynamic mass redistribution response by DMR assay F 7.2 pEC50 62.83 nM EC50 J Med Chem (2021) 64: 2634-2647 [PMID:33630609]
GPR35/G-protein coupled receptor 35 in Mouse (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2390813] [GtoPdb: 102] [UniProtKB: Q9ES90]
ChEMBL Agonist activity at mouse GPR35 expressed in CHO cells assessed as induction of beta-arrestin recruitment after 90 mins by beta-galactosidase reporter gene assay B 6.01 pEC50 980 nM EC50 J Med Chem (2013) 56: 5182-5197 [PMID:23713606]
GPR35 in Rat [GtoPdb: 102] [UniProtKB: Q33BM1]
GtoPdb - - 7.8 pEC50 - - - FEBS Lett (2006) 580: 5003-8 [PMID:16934253]
GPR35 in Human [GtoPdb: 102] [UniProtKB: Q9HC97]
GtoPdb - - 6.1 pEC50 - - - FEBS Lett (2006) 580: 5003-8 [PMID:16934253]
GPR35/G protein-coupled receptor GPR35 in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2390812] [GtoPdb: 102] [UniProtKB: Q33BM1]
ChEMBL Agonist activity at rat GPR35 expressed in CHO cells assessed as induction of beta-arrestin recruitment after 90 mins by beta-galactosidase reporter gene assay B 7.21 pEC50 61.1 nM EC50 J Med Chem (2013) 56: 5182-5197 [PMID:23713606]
GtoPdb - - 7.8 pEC50 - - - FEBS Lett (2006) 580: 5003-8 [PMID:16934253]
phosphodiesterase 10A/Phosphodiesterase 10A in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4409] [GtoPdb: 1310] [UniProtKB: Q9Y233]
ChEMBL Inhibitory concentration value against phosphodiesterase 10 B 4.66 pIC50 22000 nM IC50 J Med Chem (2005) 48: 3449-3462 [PMID:15887951]
phosphodiesterase 11A/Phosphodiesterase 11A in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2717] [GtoPdb: 1311] [UniProtKB: Q9HCR9]
ChEMBL Inhibition of human phosphodiesterase 11 B 4.92 pKi 12000 nM Ki J Med Chem (2005) 48: 3449-3462 [PMID:15887951]
phosphodiesterase 1C/Phosphodiesterase 1C in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4619] [GtoPdb: 1296] [UniProtKB: Q14123]
ChEMBL Inhibition of phosphodiesterase 1C at 100 uM B 4.89 pIC50 13000 nM IC50 J Med Chem (1994) 37: 476-485 [PMID:8120866]
phosphodiesterase 2A/Phosphodiesterase 2A in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2652] [GtoPdb: 1297] [UniProtKB: O00408]
ChEMBL Inhibition of phosphodiesterase 2 (PDE2) from porcine platelets, range 68.1-119 B 4.04 pIC50 90200 nM IC50 J Med Chem (2000) 43: 2523-2529 [PMID:10891111]
ChEMBL Inhibition of cGMP-stimulated phosphodiesterase 2 of porcine coronary arteries B 4.33 pIC50 46800 nM IC50 J Med Chem (1993) 36: 3765-3770 [PMID:8254606]
ChEMBL Inhibition of human recombinant PDE2 (phosphodiesterase 2) B 5 pIC50 >10000 nM IC50 J Med Chem (2003) 46: 4525-4532 [PMID:14521414]
phosphodiesterase 2A/Phosphodiesterase 2A in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4650] [GtoPdb: 1297] [UniProtKB: Q01062]
ChEMBL Inhibition of rat brain Phosphodiesterase 2 B 4 pIC50 100000 nM IC50 J Med Chem (1995) 38: 3547-3557 [PMID:7658441]
ChEMBL Inhibition of rat brain particulate cGMP phosphodiesterase B 4.2 pIC50 63100 nM IC50 J Med Chem (1982) 25: 1192-1198 [PMID:6292419]
Phosphodiesterase 3A in Pig (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3061] [UniProtKB: Q9XSW7]
ChEMBL Inhibition of phosphodiesterase 3 (PDE3) from porcine platelets B 4 pIC50 >100000 nM IC50 J Med Chem (2000) 43: 2523-2529 [PMID:10891111]
ChEMBL Inhibition of cGMP-inhibited phosphodiesterase from porcine coronary arteries B 4 pIC50 >100000 nM IC50 J Med Chem (1993) 36: 3765-3770 [PMID:8254606]
Phosphodiesterase 3B in Bovine (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5129] [UniProtKB: E1BN64]
ChEMBL Inhibition of bovine aorta PDE3 (phosphodiesterase 3) B 5 pIC50 >10000 nM IC50 J Med Chem (2003) 46: 4525-4532 [PMID:14521414]
phosphodiesterase 4A/Phosphodiesterase 4A in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL254] [GtoPdb: 1300] [UniProtKB: P27815]
ChEMBL Inhibition of [3H]cAMP binding to recombinant human Phosphodiesterase 4AL (PDE4AL) in baculovirus expression system B 4.3 pKi >50000 nM Ki J Med Chem (2005) 48: 1237-1243 [PMID:15715490]
Phosphodiesterase 4A in Pig (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3333] [UniProtKB: O77823]
ChEMBL Inhibition of phosphodiesterase 4 (PDE4) from porcine liver B 4 pIC50 >100000 nM IC50 J Med Chem (2000) 43: 2523-2529 [PMID:10891111]
ChEMBL Inhibition of cAMP specific phosphodiesterase from porcine aorta B 4.1 pIC50 79600 nM IC50 J Med Chem (1993) 36: 3765-3770 [PMID:8254606]
phosphodiesterase 4B/Phosphodiesterase 4B in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL275] [GtoPdb: 1301] [UniProtKB: Q07343]
ChEMBL Inhibition of [3H]cAMP binding to recombinant human Phosphodiesterase 4BL (PDE4BL) in baculovirus expression system B 4.3 pKi >50000 nM Ki J Med Chem (2005) 48: 1237-1243 [PMID:15715490]
phosphodiesterase 4D/Phosphodiesterase 4D in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL288] [GtoPdb: 1303] [UniProtKB: Q08499]
ChEMBL Inhibition of [3H]cAMP binding to recombinant human Phosphodiesterase 4DE (PDE4DE) in baculovirus expression system B 4.3 pKi >50000 nM Ki J Med Chem (2005) 48: 1237-1243 [PMID:15715490]
ChEMBL Inhibition of [3H]cAMP binding to recombinant human Phosphodiesterase 4D3 (PDE4D3) in baculovirus expression system B 4.3 pKi >50000 nM Ki J Med Chem (2005) 48: 1237-1243 [PMID:15715490]
ChEMBL Inhibition of [3H]cAMP binding to recombinant human Phosphodiesterase 4D5 (PDE4D5) in baculovirus expression system B 5.06 pKi 8760 nM Ki J Med Chem (2005) 48: 1237-1243 [PMID:15715490]
phosphodiesterase 5A/Phosphodiesterase 5A in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1827] [GtoPdb: 1304] [UniProtKB: O76074]
ChEMBL Inhibition of human phosphodiesterase 5 B 6.89 pKi 130 nM Ki J Med Chem (2005) 48: 3449-3462 [PMID:15887951]
ChEMBL Inhibition of PDE5 (unknown origin) B 5.5 pIC50 3162.28 nM IC50 J Med Chem (2018) 61: 6421-6467 [PMID:29620890]
ChEMBL Inhibitory activity against phosphodiesterase 5 from human platelets B 5.57 pIC50 2700 nM IC50 J Med Chem (1995) 38: 3547-3557 [PMID:7658441]
ChEMBL Inhibition of PDE5 (unknown origin) B 5.7 pIC50 2000 nM IC50 J Med Chem (2018) 61: 6421-6467 [PMID:29620890]
ChEMBL Inhibition of Phosphodiesterase 5 from human corpus cavernosum B 5.7 pIC50 2000 nM IC50 Bioorg Med Chem Lett (1996) 6: 1819-1824
ChEMBL Inhibition of PDE5 B 5.7 pIC50 1995.26 nM IC50 Bioorg Med Chem (2008) 16: 7599-7606 [PMID:18656371]
ChEMBL DRUGMATRIX: Phosphodiesterase PDE5 enzyme inhibition (substrate: [3H]cGMP + cGMP) B 5.87 pIC50 1349 nM IC50 DrugMatrix in vitro pharmacology data
ChEMBL Inhibition of phosphodiesterase 5 (PDE5) from porcine platelets, range 0.733-1.68 B 5.95 pIC50 1110 nM IC50 J Med Chem (2000) 43: 2523-2529 [PMID:10891111]
ChEMBL In vitro inhibition of PDE-V isolated from porcine pulmonary artery. B 6 pIC50 1000 nM IC50 J Med Chem (1993) 36: 1387-1392 [PMID:8388468]
ChEMBL Concentration required to inhibit 50% activity of phosphodiesterase VA isoenzyme at 100 uM B 6.05 pIC50 900 nM IC50 J Med Chem (1994) 37: 476-485 [PMID:8120866]
ChEMBL Inhibitory activity against cyclic GMP-phosphodiesterase (PDE V) isolated from porcine aorta. B 6.35 pIC50 450 nM IC50 J Med Chem (1993) 36: 3765-3770 [PMID:8254606]
ChEMBL In vitro inhibition of phosphodiesterase (PDE V). B 6.52 pIC50 300 nM IC50 Bioorg Med Chem Lett (1997) 7: 89-94
ChEMBL Inhibition of Phosphodiesterase 5 from human B 6.7 pIC50 200 nM IC50 J Med Chem (1996) 39: 1635-1644 [PMID:8648603]
GtoPdb - - 6.8 pIC50 158 nM IC50 Mol Pharmacol (1999) 56: 124-30 [PMID:10385692]
Phosphodiesterase 5A in Dog (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2304402] [UniProtKB: O77746]
ChEMBL Inhibition of PDE5 (unknown origin) B 6.12 pIC50 760 nM IC50 J Med Chem (2013) 56: 5182-5197 [PMID:23713606]
Phosphodiesterase 5A in Bovine (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3478] [UniProtKB: Q28156]
ChEMBL Inhibition of bovine platelet PDE5 B 6.22 pIC50 600 nM IC50 Bioorg Med Chem Lett (2012) 22: 3983-3987 [PMID:22607677]
ChEMBL Evaluated for inhibitory activity against Phosphodiesterase 5 (PDE5) purified from bovine lung B 6.3 pIC50 500 nM IC50 J Med Chem (1997) 40: 2196-2210 [PMID:9216839]
ChEMBL Inhibition of bovine aortic smooth muscle PDE5 using cGMP as substrate incubated for 30 mins in presence of EGTA and [3H]cGMP by liquid scintillation counting method B 6.52 pIC50 300 nM IC50 Eur J Med Chem (2019) 177: 269-290 [PMID:31158744]
ChEMBL Inhibitory activity against bovine PDE5 (phosphodiesterase-5). B 6.7 pIC50 200 nM IC50 J Med Chem (2003) 46: 4525-4532 [PMID:14521414]
phosphodiesterase 5A/Phosphodiesterase 5A in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4567] [GtoPdb: 1304] [UniProtKB: O54735]
ChEMBL Compound was tested for inhibition of stimulation of rat aortic smooth muscle cells (RSMC) F 5.05 pEC50 9000 nM EC50 J Med Chem (1996) 39: 1635-1644 [PMID:8648603]
phosphodiesterase 9A/Phosphodiesterase 9A in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3535] [GtoPdb: 1309] [UniProtKB: O76083]
ChEMBL Inhibition of human phosphodiesterase 9 B 4.46 pKi 35000 nM Ki J Med Chem (2005) 48: 3449-3462 [PMID:15887951]
GtoPdb - - 4.5 pIC50 31600 nM IC50 J Biol Chem (1998) 273: 15559-64 [PMID:9624146]
Plasmodium berghei (target type: ORGANISM) [ChEMBL: CHEMBL612653]
ChEMBL HARVARD: Inhibition of liver stage Plasmodium berghei infection in HepG2 cells F 5.11 pIC50 7790 nM IC50 Proc Natl Acad Sci U S A (2012) 109: 8511-8516 [PMID:22586124]
Plasmodium falciparum (target type: ORGANISM) [ChEMBL: CHEMBL364]
ChEMBL HARVARD: Inhibition of blood stage Plasmodium falciparum 3D7 infection F 4.3 pIC50 >50000 nM IC50 Proc Natl Acad Sci U S A (2012) 109: 8511-8516 [PMID:22586124]
ChEMBL Antiplasmodial activity against chloroquine-susceptible Plasmodium falciparum GHA strain infected in human erythrocytes after 72 hrs by spectrophotometry F 4.46 pIC50 35000 nM IC50 J Med Chem (2011) 54: 3222-3240 [PMID:21504142]
ChEMBL HARVARD: Inhibition of blood stage Plasmodium falciparum Dd2 infection F 4.71 pIC50 19300 nM IC50 Proc Natl Acad Sci U S A (2012) 109: 8511-8516 [PMID:22586124]
ChEMBL Antiplasmodial activity against Plasmodium falciparum GB4 after 72 hrs by SYBR green assay F 4.9 pIC50 12589.25 nM IC50 Nat Chem Biol (2009) 5: 765-771 [PMID:19734910]
ChEMBL Antiplasmodial activity against Plasmodium falciparum 3D7 after 72 hrs by SYBR green assay F 5 pIC50 10000 nM IC50 Nat Chem Biol (2009) 5: 765-771 [PMID:19734910]
mitochondrial pyruvate carrier 2 in Human [GtoPdb: 3023] [UniProtKB: O95563]
GtoPdb - - 6.52 pIC50 300 nM IC50 Mol Metab (2022) 60: 101469 [PMID:35278701]

ChEMBL data shown on this page come from version 32:

Mendez D, Gaulton A, Bento AP, Chambers J, De Veij M, Félix E, Magariños MP, Mosquera JF, Mutowo P, Nowotka M, Gordillo-Marañón M, Hunter F, Junco L, Mugumbate G, Rodriguez-Lopez M, Atkinson F, Bosc N, Radoux CJ, Segura-Cabrera A, Hersey A, Leach AR. (2019) 'ChEMBL: towards direct deposition of bioassay data' Nucleic Acids Res., 47(D1). DOI: 10.1093/nar/gky1075. [EPMCID:30398643]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]