lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Nc1ccc2ccc(COc3cccnc3)cc2n1
InChIKey: QJTDCQJZJFACPC-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 251.29, ALogP 2.79, HBA 4, HBD 1, PSA 61.03, QED 0.78
Compound (SMILES): CNCc1cc(OCc2ccc3ccc(N)nc3c2)ccc1Cl
InChIKey: SVDORCPNIHFYFA-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
Assay: Inhibition of recombinant rat nNOS expressed in Escherichia coli using L-arginine as substrate after 30 secs by hemoglobin capture assay
Measurement: Ki = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 327.82, ALogP 3.77, HBA 4, HBD 2, PSA 60.17, QED 0.75
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5ccccc5)cccc4c3)n2)c1
InChIKey: KOFXELGVKHKUJR-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human recombinant PDGFRbeta using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.6, ALogP 5.96, HBA 7, HBD 2, PSA 110.28, QED 0.26
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccc(F)c5)cccc4c3)n2)c1
InChIKey: GUUYUIDTJAWAHO-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human recombinant PDGFRbeta using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 542.59, ALogP 6.1, HBA 7, HBD 2, PSA 110.28, QED 0.24
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccnc5)cccc4c3)n2)c1
InChIKey: HAWQJVUHZAYNCF-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human recombinant PDGFRbeta using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 = 223.9 nM (pChEMBL 6.650000095367432)
Descriptors: MW 525.59, ALogP 5.36, HBA 8, HBD 2, PSA 123.17, QED 0.28
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: NS3 (SINGLE PROTEIN), West Nile virus
UniProt: K4FQI5
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets West Nile NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on West Nile virus (strain NY-99) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 11586 nM (pChEMBL 4.940000057220459)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): COCCCN1C[C@@H]2[C@@H](CNC(=O)c3nc(C(C)C)n4ccccc34)[C@@H]2C1
InChIKey: PIWCAMJYLCDVQL-OSYLJGHBSA-N
Target: 5-hydroxytryptamine receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13639
Assay: Agonist activity at human 5-HT4D receptor assessed as cAMP level after 4 hrs by luciferase reporter gene assay
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 370.5, ALogP 2.4, HBA 5, HBD 1, PSA 58.87, QED 0.73
Compound (SMILES): COc1cc(Br)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: PZAJISDCIZCGIB-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of human PDE4A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 401.24, ALogP 4.47, HBA 5, HBD 0, PSA 52.31, QED 0.47
Compound (SMILES): COc1cc(-c2ccc(F)nc2)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: OTKDXQUDAQCPRM-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of human PDE4A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 417.42, ALogP 4.91, HBA 6, HBD 0, PSA 65.2, QED 0.39
Compound (SMILES): COc1cc(Br)cc2c1nc(C)c1c(C)nc(-c3cccnc3F)n12
InChIKey: RMWWNYKNAPEPNW-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of human PDE4A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 401.24, ALogP 4.47, HBA 5, HBD 0, PSA 52.31, QED 0.47
Compound (SMILES): COc1cc(-c2cccnc2)cc2c1nc(C)c1c(C)nc(-c3cccnc3)n12
InChIKey: JOJOWCOCCMULDU-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of human PDE4A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 381.44, ALogP 4.63, HBA 6, HBD 0, PSA 65.2, QED 0.46
Compound (SMILES): COc1cc(-c2ccc(F)nc2)cc2c1nc(C)c1c(C)nc(-c3ccncc3)n12
InChIKey: VEYWHNZHTOXBLT-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of human PDE4A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 841 nM (pChEMBL 6.074999809265137)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2ccc(F)nc2)cc2c1nc(C)c1c(C)nc(-c3cccnc3)n12
InChIKey: ZTLRRRPDWBCINJ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of human PDE4A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2ccncc2)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: JAWKANDWMZNIHM-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of human PDE4A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2cccnc2)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: MTAOOMYAOJQXKB-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of human PDE4A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2cccnc2)cc2c1nc(C)c1c(C)nc(-c3cccnc3F)n12
InChIKey: JOKHDDDMDHGDNV-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of human PDE4A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): CCCCNC(=O)c1ccn2c(NCc3ccc(NC(=N)N)cc3)cnc2c1
InChIKey: BEACCZKINFJRSI-UHFFFAOYSA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Inhibition of human plasma plasmin using pyroGlu-Pro-Arg-pNA-HCl as substrate measured for 5 mins by spectrophotometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 379.47, ALogP 2.78, HBA 5, HBD 5, PSA 120.33, QED 0.23
Compound (SMILES): Cc1cc(Cl)c(OCCO)cc1NC(=O)C1=CNC(=O)C[C@H]1c1ccc(F)cc1
InChIKey: GGNOURYPUNZEOQ-HNNXBMFYSA-N
Target: P2X2/P2X3 heterotrimeric receptor (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBL9
Assay: Inhibition of P2X2/3R (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 418.85, ALogP 3.28, HBA 4, HBD 3, PSA 87.66, QED 0.67
Compound (SMILES): Cc1cc(F)c(-c2ccnn(C)c2=O)cc1NC(=O)C1=CN(C)C(=O)C[C@H]1c1ccc(F)cc1
InChIKey: GKXJURJNRHYYSL-SFHVURJKSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9 by fluorescence assay
Measurement: IC50 > 32000 nM (pChEMBL 4.494999885559082)
Descriptors: MW 464.47, ALogP 3.5, HBA 5, HBD 1, PSA 84.3, QED 0.64
Compound (SMILES): COC[C@H](O)Cn1c(=O)cnn(-c2ccc(C)c(NC(=O)C3=CN(C)C(=O)C[C@H]3c3ccc(F)cc3)c2)c1=O
InChIKey: AXCQGTYDWZDCCM-RTWAWAEBSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9 by fluorescence assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 537.55, ALogP 1.32, HBA 9, HBD 2, PSA 135.76, QED 0.44
Compound (SMILES): Cc1ccc(C(=O)O)c(C)c1NC(=O)c1cc(-c2cccc(Cl)c2)cc2ccccc12
InChIKey: SIIGKILIYGRIJN-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Antagonist activity at human EP2 receptor
Measurement: Ki = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 429.9, ALogP 6.73, HBA 2, HBD 2, PSA 66.4, QED 0.38
Compound (SMILES): CC(C)(C)OC(=O)ON(C(=O)CCCCCCC(=O)N(OC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
InChIKey: WSBNJHLXNBKHKI-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 in human HeLa cells assessed as inhibition of tubulin deacetylation incubated for overnight by cELISA
Measurement: EC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 604.69, ALogP 6.59, HBA 12, HBD 0, PSA 164.28, QED 0.13
Compound (SMILES): O=C(c1sc2c([N+](=O)[O-])cc(C(F)(F)F)cc2[n+]1[O-])N1CCCCC1
InChIKey: QIUDGPMBSANNDL-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human recombinant CYP1A2 by fluorescence assay
Measurement: IC50 = 14700 nM (pChEMBL 4.829999923706055)
Descriptors: MW 375.33, ALogP 3.09, HBA 5, HBD 0, PSA 90.39, QED 0.35
Compound (SMILES): O=C([C@@H]1COC(c2nc3cc(C(F)(F)F)cc([N+](=O)[O-])c3s2)=N1)N1CCCC1
InChIKey: WVVNCJKZXNGUEA-JTQLQIEISA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human recombinant CYP3A4 by fluorescence assay
Measurement: IC50 = 18600 nM (pChEMBL 4.730000019073486)
Descriptors: MW 414.37, ALogP 2.99, HBA 7, HBD 0, PSA 97.93, QED 0.57
Compound (SMILES): Cc1c(C(F)(F)F)cc2nc(C3=N[C@H](C(=O)N4CCCC4)CO3)sc2c1[N+](=O)[O-]
InChIKey: UIZMQOXMTKEZDN-NSHDSACASA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human recombinant CYP3A4 by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 428.39, ALogP 3.3, HBA 7, HBD 0, PSA 97.93, QED 0.55
Compound (SMILES): O=C(Nc1ccccc1C(=O)O)c1ccc2c(c1)C(=O)OC2=O
InChIKey: PGBRLTJLKQAASK-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 228.4 nM (pChEMBL 6.639999866485596)
Descriptors: MW 311.25, ALogP 1.95, HBA 5, HBD 2, PSA 109.77, QED 0.66
Compound (SMILES): O=C(Nc1ccc(Cl)cc1C(=O)O)c1ccc2c(c1)C(=O)OC2=O
InChIKey: PVLGBXMEDNNLRH-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 43.7 nM (pChEMBL 7.360000133514404)
Descriptors: MW 345.69, ALogP 2.6, HBA 5, HBD 2, PSA 109.77, QED 0.65
Compound (SMILES): COc1cc(NC(=O)c2ccc3c(c2)C(=O)OC3=O)c(C(=O)O)cc1OC
InChIKey: WDOPRGZLPROWOP-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 46.5 nM (pChEMBL 7.329999923706055)
Descriptors: MW 371.3, ALogP 1.96, HBA 7, HBD 2, PSA 128.23, QED 0.6
Compound (SMILES): O=C(Nc1ccc(I)cc1C(=O)O)c1ccc2c(c1)C(=O)OC2=O
InChIKey: DXQBWMIOVSYYKC-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 57.4 nM (pChEMBL 7.239999771118164)
Descriptors: MW 437.14, ALogP 2.55, HBA 5, HBD 2, PSA 109.77, QED 0.43
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)C(=O)OC3=O)c(C(=O)O)c1
InChIKey: KMXVWNSZSJZBRK-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 40.8 nM (pChEMBL 7.389999866485596)
Descriptors: MW 325.28, ALogP 2.26, HBA 5, HBD 2, PSA 109.77, QED 0.66
Compound (SMILES): NS(=O)(=O)c1ccc(N2C(=O)c3ccc(C(=O)Nc4ccccc4C(=O)O)cc3C2=O)cc1
InChIKey: DRMHRGCMQGYMGV-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 44.4 nM (pChEMBL 7.349999904632568)
Descriptors: MW 465.44, ALogP 2.09, HBA 6, HBD 3, PSA 163.94, QED 0.49
Compound (SMILES): NS(=O)(=O)c1ccc(CN2C(=O)c3ccc(C(=O)Nc4ccccc4C(=O)O)cc3C2=O)cc1
InChIKey: KJLIUNMQXVHGKJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 28.5 nM (pChEMBL 7.539999961853027)
Descriptors: MW 479.47, ALogP 2.08, HBA 6, HBD 3, PSA 163.94, QED 0.46
Compound (SMILES): NS(=O)(=O)c1ccc(CCN2C(=O)c3ccc(C(=O)Nc4ccccc4C(=O)O)cc3C2=O)cc1
InChIKey: AQAHXHQTCBKILC-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 493.5, ALogP 2.12, HBA 6, HBD 3, PSA 163.94, QED 0.42
Compound (SMILES): O=C(Nc1ccccc1C(=O)O)c1ccc2c(c1)C(=O)N(c1ccccc1)C2=O
InChIKey: RGRFEPRNSJRTHK-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 51.9 nM (pChEMBL 7.289999961853027)
Descriptors: MW 386.36, ALogP 3.44, HBA 4, HBD 2, PSA 103.78, QED 0.67
Compound (SMILES): O=C(Nc1ccccc1C(=O)O)c1ccc2c(c1)C(=O)N(Cc1ccccc1)C2=O
InChIKey: GQEVVWHZGOCRCN-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 27.3 nM (pChEMBL 7.559999942779541)
Descriptors: MW 400.39, ALogP 3.43, HBA 4, HBD 2, PSA 103.78, QED 0.64
Compound (SMILES): O=C(Nc1ccccc1C(=O)O)c1ccc2c(c1)C(=O)N(CCc1ccccc1)C2=O
InChIKey: YWBXPSSBGBQOQI-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 48.9 nM (pChEMBL 7.309999942779541)
Descriptors: MW 414.42, ALogP 3.48, HBA 4, HBD 2, PSA 103.78, QED 0.6
Compound (SMILES): O=C(O)c1ccc(N2C(=O)c3ccc(C(=O)Nc4ccccc4C(=O)O)cc3C2=O)cc1
InChIKey: HZBPRFOEZIPHPY-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 56.4 nM (pChEMBL 7.25)
Descriptors: MW 430.37, ALogP 3.14, HBA 5, HBD 3, PSA 141.08, QED 0.53
Compound (SMILES): CCOC(=O)c1ccc(N2C(=O)c3ccc(C(=O)Nc4ccccc4C(=O)O)cc3C2=O)cc1
InChIKey: FTWATXICDVIBPN-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase-12 preincubated for 15 mins by stopped flow CO2 dehydration assay
Measurement: Ki = 18.5 nM (pChEMBL 7.730000019073486)
Descriptors: MW 458.43, ALogP 3.61, HBA 6, HBD 2, PSA 130.08, QED 0.43
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at S1P5 receptor (unknown origin) expressed in CHO cell membranes after 30 mins by GTPgammaS binding assay
Measurement: EC50 = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=S)Nc2ccc(-c3c4ccc(=O)cc-4oc4cc(O)ccc34)c(C(=O)O)c2)cc1
InChIKey: MWYSNECAHMAFGG-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human carbonic anhydrase-14 preincubated for 15 mins by stopped flow CO2 dehydration method
Measurement: Ki = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 575.62, ALogP 4.1, HBA 7, HBD 5, PSA 171.96, QED 0.15
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(CNC(=S)Nc3ccc(-c4c5ccc(=O)cc-5oc5cc(O)ccc45)c(C(=O)O)c3)nn2)cc1
InChIKey: YKWZALQMWYUDGJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human carbonic anhydrase-14 preincubated for 15 mins by stopped flow CO2 dehydration method
Measurement: Ki = 12.8 nM (pChEMBL 7.889999866485596)
Descriptors: MW 642.67, ALogP 3.68, HBA 10, HBD 5, PSA 202.67, QED 0.13
Compound (SMILES): NS(=O)(=O)c1cccc(-n2cc(CNC(=S)Nc3ccc(-c4c5ccc(=O)cc-5oc5cc(O)ccc45)c(C(=O)O)c3)nn2)c1
InChIKey: LNCLRLKBMUZUDO-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human carbonic anhydrase-14 preincubated for 15 mins by stopped flow CO2 dehydration method
Measurement: Ki = 53.6 nM (pChEMBL 7.269999980926514)
Descriptors: MW 642.67, ALogP 3.68, HBA 10, HBD 5, PSA 202.67, QED 0.13
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(NC(=S)NCc4cn(-c5cccc(S(N)(=O)=O)c5)nn4)cc3C(=O)O)c3ccc(=[N+](C)C)cc-3oc2c1.[Cl-]
InChIKey: BLRCKCWMBZMDBH-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human carbonic anhydrase-14 preincubated for 15 mins by stopped flow CO2 dehydration method
Measurement: Ki = 31.4 nM (pChEMBL 7.5)
Descriptors: MW 697.82, ALogP 3.72, HBA 9, HBD 4, PSA 171.62, QED 0.1
Compound (SMILES): O=C(O)C(=O)O.c1ccc(OCCNC[C@H]2COC(c3ccccc3)(c3ccccc3)O2)cc1
InChIKey: JAHHZJFOTROQSY-BQAIUKQQSA-N
Target: Alpha-1D adrenergic receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23944
Assay: Antagonist activity at alpha1D adrenoceptor in Wistar rat thoracic aorta assessed as noradrenaline-induced contractions after 30 mins
Measurement: Kd = 24.55 nM (pChEMBL 7.610000133514404)
Descriptors: MW 375.47, ALogP 3.97, HBA 4, HBD 1, PSA 39.72, QED 0.6
Compound (SMILES): O=C(O)C(=O)O.c1ccc(OCCNC[C@@H]2COC(c3ccccc3)(c3ccccc3)O2)cc1
InChIKey: JAHHZJFOTROQSY-GNAFDRTKSA-N
Target: Alpha-1D adrenergic receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23944
Assay: Antagonist activity at alpha1D adrenoceptor in Wistar rat thoracic aorta assessed as noradrenaline-induced contractions after 30 mins
Measurement: Kd = 5.129 nM (pChEMBL 8.289999961853027)
Descriptors: MW 375.47, ALogP 3.97, HBA 4, HBD 1, PSA 39.72, QED 0.6
Compound (SMILES): CCOC(=O)C1=C(CN2CCOCC2)NC(c2nccs2)=NC1c1ccc(F)cc1Br
InChIKey: SQGRDKSRFFUBBU-UHFFFAOYSA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Inhibition of reverse transcriptase M204I mutant expressing telbivudine-resistant hepatitis B virus capsid assembly in human Huh7 cells assessed as reduction in intracellular DNA levels measured on day 7 by real-time PCR analysis
Measurement: EC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 509.4, ALogP 3.29, HBA 8, HBD 1, PSA 76.05, QED 0.6
Compound (SMILES): O=S(=O)(c1ccc(C(F)(F)F)cc1)N1CCC(CN2CCC(c3noc4cc(F)ccc34)CC2)CC1
InChIKey: LIHYUCWMNKTEOX-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P31389
Assay: Displacement of [3H]mepyramine from histamine H1 receptor in guinea pig cerebellum
Measurement: Ki = 43.6 nM (pChEMBL 7.360000133514404)
Descriptors: MW 525.57, ALogP 5.27, HBA 5, HBD 0, PSA 66.65, QED 0.43
Compound (SMILES): O=[N+]([O-])c1ccc(S(=O)(=O)N2CCC(CN3CCC(c4noc5cc(F)ccc45)CC3)CC2)cc1
InChIKey: RTIUOKVMNZFXBZ-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P31389
Assay: Displacement of [3H]mepyramine from histamine H1 receptor in guinea pig cerebellum
Measurement: Ki = 2845.2 nM (pChEMBL 5.550000190734863)
Descriptors: MW 502.57, ALogP 4.16, HBA 7, HBD 0, PSA 109.79, QED 0.37
Compound (SMILES): CC1(C)c2cc(C3CCN(CC4CCOCC4)CC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
InChIKey: VWCZORWQNKCYGE-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of N-terminal His6-tagged recombinant human IGF-1R (959 residues) expressed in insect Sf21 cells using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA
Measurement: IC50 = 27.8 nM (pChEMBL 7.559999942779541)
Descriptors: MW 467.61, ALogP 5.52, HBA 4, HBD 1, PSA 69.12, QED 0.55
Compound (SMILES): CCc1cc2c(cc1-c1cnn(C3CCOCC3)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: ZOUKGWPEJXISGG-UHFFFAOYSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of EML4-ALK F1174L mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay
Measurement: IC50 = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 464.57, ALogP 5.69, HBA 5, HBD 1, PSA 83.7, QED 0.42
Compound (SMILES): CCc1cc2c(cc1-c1cnn(C3CCNCC3)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: AGEWKUQZNAGGEC-UHFFFAOYSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of EML4-ALK L1196M mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay
Measurement: IC50 = 262 nM (pChEMBL 6.579999923706055)
Descriptors: MW 463.59, ALogP 5.26, HBA 5, HBD 2, PSA 86.5, QED 0.43
Compound (SMILES): CCc1cc2c(cc1-c1cnn(CC(=O)N(C)C)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: IDGNCVHQDDOPND-UHFFFAOYSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of EML4-ALK F1174L mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 465.56, ALogP 4.42, HBA 5, HBD 1, PSA 94.78, QED 0.48
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cccc(F)c4F)cc23)CC1
InChIKey: QCLXNOBXQUWUEW-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of human recombinant CLK1 by LANCE assay
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 428.48, ALogP 3.6, HBA 4, HBD 2, PSA 70.25, QED 0.6
Compound (SMILES): CC1=NN(c2ccc(C(=O)O)cc2)C(=O)/C1=C/c1ccc(-c2cc(C)c(C)cc2[N+](=O)[O-])o1
InChIKey: HEKJYZZSCQBJGB-XDHOZWIPSA-N
Target: CREB-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q92793
Assay: Inhibition of CBP BHC domain (unknown origin)
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 445.43, ALogP 4.98, HBA 6, HBD 1, PSA 126.25, QED 0.34
Compound (SMILES): CN(C)Cc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: NTASSNARMLLQTN-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 2080 nM (pChEMBL 5.679999828338623)
Descriptors: MW 307.4, ALogP 3.46, HBA 4, HBD 1, PSA 51.38, QED 0.78
Compound (SMILES): Nc1ccc2ccc(COc3cccnc3)cc2n1
InChIKey: QJTDCQJZJFACPC-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z0J4
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 16800 nM (pChEMBL 4.78000020980835)
Descriptors: MW 251.29, ALogP 2.79, HBA 4, HBD 1, PSA 61.03, QED 0.78
Compound (SMILES): CNCc1cc(OCc2ccc3ccc(N)nc3c2)ccc1Cl
InChIKey: SVDORCPNIHFYFA-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 32 nM (pChEMBL 7.5)
Descriptors: MW 327.82, ALogP 3.77, HBA 4, HBD 2, PSA 60.17, QED 0.75
Compound (SMILES): CNCc1cncc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: CCVIETYDINGXSM-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 5790 nM (pChEMBL 5.239999771118164)
Descriptors: MW 294.36, ALogP 2.51, HBA 5, HBD 2, PSA 73.06, QED 0.76
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5ccccc5)cccc4c3)n2)c1
InChIKey: KOFXELGVKHKUJR-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of human recombinant RET using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 = 59.2 nM (pChEMBL 7.230000019073486)
Descriptors: MW 524.6, ALogP 5.96, HBA 7, HBD 2, PSA 110.28, QED 0.26
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccc(F)c5)cccc4c3)n2)c1
InChIKey: GUUYUIDTJAWAHO-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of human recombinant RET using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 = 22.8 nM (pChEMBL 7.639999866485596)
Descriptors: MW 542.59, ALogP 6.1, HBA 7, HBD 2, PSA 110.28, QED 0.24
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccnc5)cccc4c3)n2)c1
InChIKey: HAWQJVUHZAYNCF-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of human recombinant RET using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 = 167.1 nM (pChEMBL 6.78000020980835)
Descriptors: MW 525.59, ALogP 5.36, HBA 8, HBD 2, PSA 123.17, QED 0.28
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Zika NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Zika virus (strain PRVABC59) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 19360 nM (pChEMBL 4.710000038146973)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): COCCCN1C[C@@H]2[C@@H](CNC(=O)c3nc(C(C)C)n4ccccc34)[C@@H]2C1
InChIKey: PIWCAMJYLCDVQL-OSYLJGHBSA-N
Target: 5-hydroxytryptamine receptor 4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62758
Assay: Agonist activity at rat 5-HT4L receptor assessed as cAMP level after 4 hrs by luciferase reporter gene assay
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 370.5, ALogP 2.4, HBA 5, HBD 1, PSA 58.87, QED 0.73
Compound (SMILES): COc1cc(Br)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: PZAJISDCIZCGIB-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 401.24, ALogP 4.47, HBA 5, HBD 0, PSA 52.31, QED 0.47
Compound (SMILES): COc1cc(-c2ccc(F)nc2)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: OTKDXQUDAQCPRM-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 417.42, ALogP 4.91, HBA 6, HBD 0, PSA 65.2, QED 0.39
Compound (SMILES): COc1cc(Br)cc2c1nc(C)c1c(C)nc(-c3cccnc3F)n12
InChIKey: RMWWNYKNAPEPNW-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 606 nM (pChEMBL 6.21999979019165)
Descriptors: MW 401.24, ALogP 4.47, HBA 5, HBD 0, PSA 52.31, QED 0.47
Compound (SMILES): COc1cc(-c2cccnc2)cc2c1nc(C)c1c(C)nc(-c3cccnc3)n12
InChIKey: JOJOWCOCCMULDU-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 232 nM (pChEMBL 6.630000114440918)
Descriptors: MW 381.44, ALogP 4.63, HBA 6, HBD 0, PSA 65.2, QED 0.46
Compound (SMILES): COc1cc(-c2ccc(F)nc2)cc2c1nc(C)c1c(C)nc(-c3ccncc3)n12
InChIKey: VEYWHNZHTOXBLT-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 201 nM (pChEMBL 6.699999809265137)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2ccc(F)nc2)cc2c1nc(C)c1c(C)nc(-c3cccnc3)n12
InChIKey: ZTLRRRPDWBCINJ-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 279 nM (pChEMBL 6.550000190734863)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2ccncc2)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: JAWKANDWMZNIHM-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 195 nM (pChEMBL 6.710000038146973)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2cccnc2)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: MTAOOMYAOJQXKB-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 228 nM (pChEMBL 6.639999866485596)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2cccnc2)cc2c1nc(C)c1c(C)nc(-c3cccnc3F)n12
InChIKey: JOKHDDDMDHGDNV-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 91.6 nM (pChEMBL 7.039999961853027)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): CCCCNC(=O)c1ccn2c(NCc3ccc(NC(=N)N)cc3)cnc2c1
InChIKey: BEACCZKINFJRSI-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using D-Pro-Phe-Arg-pNA-2HCl as substrate measured for 5 mins by spectrophotometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 379.47, ALogP 2.78, HBA 5, HBD 5, PSA 120.33, QED 0.23
Compound (SMILES): Cc1cc(Cl)c(OCCO)cc1NC(=O)C1=CNC(=O)C[C@H]1c1ccc(F)cc1
InChIKey: GGNOURYPUNZEOQ-HNNXBMFYSA-N
Target: P2X purinoceptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99571
Assay: Inhibition of P2X4R (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 418.85, ALogP 3.28, HBA 4, HBD 3, PSA 87.66, QED 0.67
Compound (SMILES): Cc1ccc(C(=O)O)c(C)c1NC(=O)c1cc(-c2cccc(Cl)c2)cc2ccccc12
InChIKey: SIIGKILIYGRIJN-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Antagonist activity at human EP3 receptor
Measurement: Ki > 17500 nM (pChEMBL 4.756999969482422)
Descriptors: MW 429.9, ALogP 6.73, HBA 2, HBD 2, PSA 66.4, QED 0.38
Compound (SMILES): O=C(Nc1ccc(Cl)cc1C(=O)O)c1ccc2c(c1)C(=O)OC2=O
InChIKey: PVLGBXMEDNNLRH-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human CA1 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 345.69, ALogP 2.6, HBA 5, HBD 2, PSA 109.77, QED 0.65
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at S1P5 receptor (unknown origin) expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation by GTPgammaS binding assay
Measurement: EC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): CCOC(=O)C1=C(CN2CCOCC2)NC(c2nccs2)=NC1c1ccc(F)cc1Br
InChIKey: SQGRDKSRFFUBBU-UHFFFAOYSA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Inhibition of reverse transcriptase M204I/V173L double mutant expressing lamivudine-resistant hepatitis B virus capsid assembly in human Huh7 cells assessed as reduction in secreted DNA levels measured on day 7 by real-time PCR analysis
Measurement: EC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 509.4, ALogP 3.29, HBA 8, HBD 1, PSA 76.05, QED 0.6
Compound (SMILES): O=S(=O)(c1ccc(C(F)(F)F)cc1)N1CCC(CN2CCC(c3noc4cc(F)ccc34)CC2)CC1
InChIKey: LIHYUCWMNKTEOX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08909
Assay: Displacement of [3H]mesulergine from 5HT2C receptor in rat brain cortex
Measurement: Ki = 136.8 nM (pChEMBL 6.860000133514404)
Descriptors: MW 525.57, ALogP 5.27, HBA 5, HBD 0, PSA 66.65, QED 0.43
Compound (SMILES): O=[N+]([O-])c1ccc(S(=O)(=O)N2CCC(CN3CCC(c4noc5cc(F)ccc45)CC3)CC2)cc1
InChIKey: RTIUOKVMNZFXBZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08909
Assay: Displacement of [3H]mesulergine from 5HT2C receptor in rat brain cortex
Measurement: Ki = 998.2 nM (pChEMBL 6)
Descriptors: MW 502.57, ALogP 4.16, HBA 7, HBD 0, PSA 109.79, QED 0.37
Compound (SMILES): CC1(C)c2cc(C3CCN(CC4CCOCC4)CC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
InChIKey: VWCZORWQNKCYGE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of recombinant human AXL using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 467.61, ALogP 5.52, HBA 4, HBD 1, PSA 69.12, QED 0.55
Compound (SMILES): CCc1cc2c(cc1-c1cnn(C3CCOCC3)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: ZOUKGWPEJXISGG-UHFFFAOYSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 464.57, ALogP 5.69, HBA 5, HBD 1, PSA 83.7, QED 0.42
Compound (SMILES): CCc1cc2c(cc1-c1cnn(C3CCNCC3)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: AGEWKUQZNAGGEC-UHFFFAOYSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of EML4-ALK F1174L mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay
Measurement: IC50 = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 463.59, ALogP 5.26, HBA 5, HBD 2, PSA 86.5, QED 0.43
Compound (SMILES): CCc1cc2c(cc1-c1cnn(CC(=O)N(C)C)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: IDGNCVHQDDOPND-UHFFFAOYSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of EML4-ALK C1156Y mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 465.56, ALogP 4.42, HBA 5, HBD 1, PSA 94.78, QED 0.48
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cccc(F)c4F)cc23)CC1
InChIKey: QCLXNOBXQUWUEW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: Inhibition of human recombinant LynB by LANCE assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 428.48, ALogP 3.6, HBA 4, HBD 2, PSA 70.25, QED 0.6
Compound (SMILES): CN(C)CCc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: TTZAIJYOUAIUID-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z0J4
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 33200 nM (pChEMBL 4.480000019073486)
Descriptors: MW 321.42, ALogP 3.5, HBA 4, HBD 1, PSA 51.38, QED 0.75
Compound (SMILES): CN(C)Cc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: NTASSNARMLLQTN-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 307.4, ALogP 3.46, HBA 4, HBD 1, PSA 51.38, QED 0.78