lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(CC3CC3)n2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: IYVALPSKVAMDMH-JRPXNJEYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 = 10700 nM (pChEMBL 4.96999979019165)
Descriptors: MW 501.63, ALogP 5.28, HBA 6, HBD 1, PSA 84.66, QED 0.45
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C3CC3)n2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: GDEYVKYYDNYXSM-WRONEBCDSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 = 28800 nM (pChEMBL 4.539999961853027)
Descriptors: MW 487.6, ALogP 5.21, HBA 6, HBD 1, PSA 84.66, QED 0.49
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(F)cc2F)cc1)N1CC[C@](CC(C)(C)O)(c2ccc(F)cc2)OC1=O
InChIKey: ZTMCZWXIGPCMLA-JMQGSBJISA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 483.53, ALogP 6.73, HBA 3, HBD 1, PSA 49.77, QED 0.42
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(F)cc2)cc1)N1CC[C@](CCC(N)=O)(c2ccccc2)OC1=O
InChIKey: IEUDNQIKLSMAIA-UZTOHYMASA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 = 12500 nM (pChEMBL 4.900000095367432)
Descriptors: MW 446.52, ALogP 5.56, HBA 3, HBD 1, PSA 72.63, QED 0.52
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(F)cc2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: QBTXWKOWTNTLRJ-MMTVBGGISA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 447.55, ALogP 6.45, HBA 3, HBD 1, PSA 49.77, QED 0.47
Compound (SMILES): C[C@@H](c1ccc(Br)cc1)N1CC[C@](CC(C)(C)O)(c2ccc(F)cc2)OC1=O
InChIKey: PCUYRJPAAXXRSG-NYHFZMIOSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Biological Assay Example 1: The inhibition of a microsomal preparation of 11β-HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384).
Measurement: IC50 = 0.76 nM (pChEMBL 9.119999885559082)
Descriptors: MW 450.35, ALogP 5.55, HBA 3, HBD 1, PSA 49.77, QED 0.65
Compound (SMILES): C[C@@H](c1ccc(OC(F)F)cc1)N1CC[C@](CCO)(c2ccc(F)cc2)OC1=O
InChIKey: OALZCBAIPRRJJG-QKKBWIMNSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 409.4, ALogP 4.61, HBA 4, HBD 1, PSA 59, QED 0.73
Compound (SMILES): C[C@@H](c1ccc(Br)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: DNGAQKDEHIEQAQ-AOMKIAJQSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 < 400 nM (pChEMBL 6.3979997634887695)
Descriptors: MW 432.36, ALogP 5.41, HBA 3, HBD 1, PSA 49.77, QED 0.69
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)n2)cc1)N1CC[C@](CCCO)(c2ccccc2)OC1=O
InChIKey: PGQZLXAQNFHWTD-AFMDSPMNSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 447.54, ALogP 4.02, HBA 6, HBD 1, PSA 84.66, QED 0.59
Compound (SMILES): CN(C)CC(=O)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: AKPGAWHSDHEYDD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 306.37, ALogP 2.8, HBA 4, HBD 1, PSA 58.12, QED 0.81
Compound (SMILES): O=C(CN1CCCC1)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: RVDYQNMCCLFQNH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 332.41, ALogP 3.33, HBA 4, HBD 1, PSA 58.12, QED 0.8
Compound (SMILES): O=C(CN1CCN(c2ccc(Cl)cc2)CC1)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: FNIUNMYSUAZBAG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 457.97, ALogP 4.71, HBA 5, HBD 1, PSA 61.36, QED 0.47
Compound (SMILES): O=C(CCCCl)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: PRPDRFAGTXCLHG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 325.8, ALogP 4.25, HBA 3, HBD 1, PSA 54.88, QED 0.71
Compound (SMILES): O=C(Cn1cncn1)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: LJKBEPOTPGIQNW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 330.35, ALogP 2.53, HBA 6, HBD 1, PSA 85.59, QED 0.62
Compound (SMILES): N#CCC(=O)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: GJEIGGNJDANTGV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 = 136 nM (pChEMBL 6.869999885559082)
Descriptors: MW 288.31, ALogP 3.15, HBA 4, HBD 1, PSA 78.67, QED 0.8
Compound (SMILES): O=C(CN1CCCCC1)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: KDWMCCGEVVUUSI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 346.43, ALogP 3.72, HBA 4, HBD 1, PSA 58.12, QED 0.78
Compound (SMILES): COc1ccc(NC(=O)Nc2cccc(-c3cnc4ccccc4n3)c2)cc1
InChIKey: HNYMIBDUKIOVBK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 370.41, ALogP 4.95, HBA 4, HBD 2, PSA 76.14, QED 0.53
Compound (SMILES): O=S(=O)(Nc1cccc(-c2cnc3ccccc3n2)c1)c1cccs1
InChIKey: ZVEAXJMWGAWVFV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 = 55500 nM (pChEMBL 4.260000228881836)
Descriptors: MW 367.46, ALogP 4.16, HBA 5, HBD 1, PSA 71.95, QED 0.59
Compound (SMILES): O=C(Nc1cccc(-c2cnc3ccccc3n2)c1)C1CC1
InChIKey: GGSGXXLVTMCOAS-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 289.34, ALogP 3.65, HBA 3, HBD 1, PSA 54.88, QED 0.8
Compound (SMILES): O=C(CN1CCN(c2ccccc2)CC1)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: KANPWRCCZWMBEX-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 423.52, ALogP 4.06, HBA 5, HBD 1, PSA 61.36, QED 0.52
Compound (SMILES): CN1CCN(CC(=O)Nc2cccc(-c3cnc4ccccc4n3)c2)CC1
InChIKey: RETALPAJDGZPSB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 361.45, ALogP 2.48, HBA 5, HBD 1, PSA 61.36, QED 0.77
Compound (SMILES): O=C(Nc1cccc(-c2cnc3ccccc3n2)c1)C(Cl)Cl
InChIKey: GCWQNTFVSFUHNG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 332.19, ALogP 4.04, HBA 3, HBD 1, PSA 54.88, QED 0.74
Compound (SMILES): O=C(CCCl)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: DDNQKRCESDJORY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 311.77, ALogP 3.86, HBA 3, HBD 1, PSA 54.88, QED 0.74
Compound (SMILES): O=C(CN1CCOCC1)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: IVKSMVLEKBVDAI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 348.41, ALogP 2.57, HBA 5, HBD 1, PSA 67.35, QED 0.78
Compound (SMILES): CC(Cl)C(=O)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: ZPGLKTJHUUFKFT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 311.77, ALogP 3.86, HBA 3, HBD 1, PSA 54.88, QED 0.75
Compound (SMILES): C=CC(=O)Nc1cccc(-c2cnc3ccccc3n2)c1
InChIKey: XGTXKHNTUGUVRE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Kinase Enzyme Assay: In vitro kinase enzyme assay using Jak3, Jak2, Jak1, and Tyk2.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 275.31, ALogP 3.42, HBA 3, HBD 1, PSA 54.88, QED 0.75
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(=O)(=O)C3CC3)cc2)ncc1C(F)(F)F
InChIKey: BAOWDLOLYGOWOE-GHMZBOCLSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Kinase Assay: CDK1/CycB (200 ng/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C, the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 431.44, ALogP 3.32, HBA 7, HBD 2, PSA 101.41, QED 0.69
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(C)(=O)=O)cc2)ncc1C(F)(F)F
InChIKey: JLMIHNJHBAEFKC-NXEZZACHSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Kinase Assay: CDK1/CycB (200 ng/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C, the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 405.4, ALogP 2.79, HBA 7, HBD 2, PSA 101.41, QED 0.76
Compound (SMILES): C[C@@H](Oc1nc(Nc2ccc(S(C)(=O)=O)cc2)ncc1C(F)(F)F)C(C)(C)O
InChIKey: PAEDTQQTYBULPN-SNVBAGLBSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Kinase Assay: CDK1/CycB (200 ng/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C, the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 419.43, ALogP 3.18, HBA 7, HBD 2, PSA 101.41, QED 0.74
Compound (SMILES): CC(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: PWVBXAIRJXQMCU-VEEPYNQNSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 3350 nM (pChEMBL 5.46999979019165)
Descriptors: MW 1058.22
Compound (SMILES): CCn1c(=O)c2cnc3c(Cl)cccc3c2n(C2CCCC2)c1=O
InChIKey: RNTPXDNXVJTNNP-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 343.81, ALogP 3.5, HBA 5, HBD 0, PSA 56.89, QED 0.67
Compound (SMILES): CCn1c(=O)c2cnc3c(C(C)C)cccc3c2n(C2CCCC2)c1=O
InChIKey: IWWGJHDCEUWDTE-UHFFFAOYSA-N
Target: Lipopolysaccharide-induced tumor necrosis factor-alpha factor (SINGLE PROTEIN), Homo sapiens
UniProt: Q99732
Assay: TNF inhibition assay: Samples were tested for TNF as per the manufacturer's instructions (TNF ELISA; R&D Systems, Cat #DY210). The samples were serially diluted with PBS+1% BSA to the appropriate dilution condition for the cell prep, typically a 1:4 or 1:6 dilution.
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 351.45, ALogP 3.97, HBA 5, HBD 0, PSA 56.89, QED 0.67
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3cc(C)cs3)c(=O)n(C3CCCC3)c12
InChIKey: XBMCCMKXNQMPDO-UHFFFAOYSA-N
Target: Lipopolysaccharide-induced tumor necrosis factor-alpha factor (SINGLE PROTEIN), Homo sapiens
UniProt: Q99732
Assay: TNF inhibition assay: Samples were tested for TNF as per the manufacturer's instructions (TNF ELISA; R&D Systems, Cat #DY210). The samples were serially diluted with PBS+1% BSA to the appropriate dilution condition for the cell prep, typically a 1:4 or 1:6 dilution.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 407.5, ALogP 4.19, HBA 7, HBD 0, PSA 66.12, QED 0.48
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3cccc(C)c3)c(=O)n(C3CCCC3)c12
InChIKey: NMCBQDCTQPGXHQ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 338 nM (pChEMBL 6.46999979019165)
Descriptors: MW 401.47, ALogP 4.13, HBA 6, HBD 0, PSA 66.12, QED 0.48
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3cccc(Cl)c3)c(=O)n([C@@H]3CCN(S(C)(=O)=O)C3)c12
InChIKey: QBTZSDNOQVLDBB-MRXNPFEDSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 163 nM (pChEMBL 6.789999961853027)
Descriptors: MW 500.96, ALogP 2.57, HBA 8, HBD 0, PSA 103.5, QED 0.4
Compound (SMILES): O=c1[nH]nc2c3c(cccc13)N=C(CN1Cc3ccccc3C1)N2
InChIKey: JLFSBHQQXIAQEC-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of human recombinant TNKS2 by chemiluminescent assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 317.35, ALogP 2.39, HBA 5, HBD 2, PSA 73.38, QED 0.76
Compound (SMILES): Nc1ncnc2c1ncn2[C@H]1O[C@@H](CN(CCNCCc2ccc(Cl)cc2)CC[C@H](N)C(=O)O)[C@H](O)[C@@H]1O
InChIKey: WWKSYRSOVZNFOY-HMDXBLRFSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Compound 75 was serially diluted 3 fold in DMSO for 10 points and 1 μL was plated in a 384 well microtiter plate. Positive control (100% inhibition standard) was 100 μM final concentration of SAH and negative control (0% inhibition standard) contained 1 μL of DMSO. Compound 75 was then incubated for 30 minutes with 40 μL per well of EZH2 wild-type and mutants at 8 nM in pH 7.6 assay buffer (20 mM BICINE, 100 mM KCl, 1 mM DTT, 0.002% Tween 20, 0.005% BSG). A substrate mix at 10 μL per well was added which contained 5-adenosylmethionine-Cl (SAM) at 150 nM and tritiated SAM at 100 nM, and biotinylated oligonucleosome at 150 nM in pH 7.6 assay buffer. Quenched enzyme reaction was transferred to a streptavidin-coated Flashplate (Perkin Elmer, catalog number SMP410), allowed to bind for one hour, and detected on a TopCount NXT HTS (Perkin Elmer).
Measurement: IC50 = 7560 nM (pChEMBL 5.119999885559082)
Descriptors: MW 549.03, ALogP -0.38, HBA 12, HBD 6, PSA 197.9, QED 0.15
Compound (SMILES): CCc1cc(O)c(F)cc1-c1ccc2c(-c3nc4c([nH]3)CCN(C(=O)c3ccc(F)cc3)C4)n[nH]c2c1
InChIKey: SYMXGYXFLGDULR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of GST tagged human recombinant JAK3 catalytic domain expressed in baculovirus using peptide substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by microfluidic assay
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 499.52, ALogP 5.36, HBA 4, HBD 3, PSA 97.9, QED 0.31
Compound (SMILES): CCc1cc(O)c(F)cc1-c1ccc2c(-c3nc4c([nH]3)CCN(C(=O)c3cnc(N5CCCCC5)cn3)C4)n[nH]c2c1
InChIKey: XDJGNPSZQSWJCV-UHFFFAOYSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK1/TYK2 in human whole blood lymphocytes assessed as inhibition of IFNalpha induced STAT3 phosphorylation preincubated for 45 mins followed by IFNalpha addition and measured after 20 mins by flow cytometric analysis
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 566.64, ALogP 5.01, HBA 7, HBD 3, PSA 126.92, QED 0.27
Compound (SMILES): CCOc1ccccc1-c1cccn2nc(Nc3ccc4c(c3)CCNCC4)nc12
InChIKey: LTPHZQBJCGYNFF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Enzyme Assay: The ability of compounds to inhibit the kinase activity of baculovirus-expressed human FAK and JAK kinase using the time-resolved fluorescence (TRF) assay system.
Measurement: IC50 = 130.71 nM (pChEMBL 6.880000114440918)
Descriptors: MW 399.5, ALogP 4.23, HBA 6, HBD 2, PSA 63.48, QED 0.53
Compound (SMILES): CS(=O)(=O)N1CCN(c2ccc(Nc3ncc(C(N)=O)c(NC4CC4)n3)cc2)CC1
InChIKey: PFDUPXGEXSITJW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Binding Assay: ATP-site dependent competition binding assay using Ambit KinomeScan Screening kit.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 431.52, ALogP 0.97, HBA 8, HBD 3, PSA 133.55, QED 0.59
Compound (SMILES): NC(=O)c1cnc(Nc2ccc(N3CCC[C@@H](C(N)=O)C3)cc2)nc1NC1CC1
InChIKey: UNRTWZKXADNVLM-GFCCVEGCSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Binding Assay: ATP-site dependent competition binding assay using Ambit KinomeScan Screening kit.
Measurement: Kd = 9.4 nM (pChEMBL 8.029999732971191)
Descriptors: MW 395.47, ALogP 1.6, HBA 7, HBD 4, PSA 139.26, QED 0.56
Compound (SMILES): CCOC(=O)/C=C/c1c(OC)ccc2cc(-c3cccc(OC)c3)ccc12
InChIKey: WCLQUDCFQAVYPS-ACCUITESSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: Inhibition assay using P450 CYP enzymes.
Measurement: IC50 = 1580 nM (pChEMBL 5.800000190734863)
Descriptors: MW 362.43, ALogP 5.1, HBA 4, HBD 0, PSA 44.76, QED 0.45
Compound (SMILES): O=C(O)CCC(=O)Nc1ccc(-c2c(O)ccc3cc(-c4cccc(O)c4)ccc23)cc1
InChIKey: ZTMKPXUZAMIYCW-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: Inhibition assay using P450 CYP enzymes.
Measurement: IC50 = 221 nM (pChEMBL 6.659999847412109)
Descriptors: MW 427.46, ALogP 5.39, HBA 4, HBD 4, PSA 106.86, QED 0.33
Compound (SMILES): CNC(=O)/C=C/c1cc(OC)cc(-c2ccc3cc(OC)ccc3c2)c1
InChIKey: VIZKFHFQFJRUES-RUDMXATFSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assay: Inhibition assay using P450 CYP enzymes.
Measurement: IC50 = 39350 nM (pChEMBL 4.409999847412109)
Descriptors: MW 347.41, ALogP 4.28, HBA 3, HBD 1, PSA 47.56, QED 0.7
Compound (SMILES): CC(C)(CO)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCN5CCOCC5)ccc34)cc2)no1
InChIKey: BDDKOCILLICHON-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Binding Assay: Competition binding assay used herein were developed validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336.
Measurement: Kd = 0.77 nM (pChEMBL 9.109999656677246)
Descriptors: MW 576.68, ALogP 4.83, HBA 10, HBD 3, PSA 126.39, QED 0.23
Compound (SMILES): CC(CO)(CO)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCN5CCOCC5)ccc34)cc2)no1
InChIKey: RWLXCDFZJDZLHX-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Binding Assay: Competition binding assay used herein were developed validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336.
Measurement: Kd = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 592.68, ALogP 3.8, HBA 11, HBD 4, PSA 146.62, QED 0.19
Compound (SMILES): CN(C)CCc1c[nH]c2ccc(/N=C(\N)c3cccs3)cc12
InChIKey: TZUMRJWGGAAQFU-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Enzyme Assay: Enzyme assay using recombinant human inducible NOS (iNOS), human endothelial constitutive NOS (eNOS) or human neuronal constitutive NOS (nNOS).
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 312.44, ALogP 3.37, HBA 3, HBD 2, PSA 57.41, QED 0.56
Compound (SMILES): CN1CCC(c2c[nH]c3ccc(/N=C(\N)c4cccs4)cc23)C1
InChIKey: NWUGWNUIRGACCZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Rattus norvegicus
UniProt: P28564
Assay: Binding Assay: 5-HT1D binding assays (agonist radioligand)were performed using bovine caudate membranes according to the methods of Heuring and Peroutka (J. Neurosci 1987, 7: 894-903). 5-HT1B (rat cerebral cortex) binding assays (agonist radioligand) were performed according to the method of Hoyer et. al. (Eur. J. Pharmacol. 1995, 118: 1-12).
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 324.45, ALogP 3.69, HBA 3, HBD 2, PSA 57.41, QED 0.57
Compound (SMILES): N[C@H]1C[C@@H](N2Cc3cnn(S(=O)(=O)C4CCCC4)c3C2)CO[C@@H]1c1cc(F)ccc1F
InChIKey: OQYMNVVXGACVAN-MFMILTCTSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of DPP-4 (unknown origin)
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 452.53, ALogP 2.45, HBA 7, HBD 1, PSA 90.45, QED 0.77
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)n2)cc1)N1CC[C@](CC(C)(C)O)(c2ccc(F)cc2)OC1=O
InChIKey: INMWFVJXYNMTDV-MYUZEXMDSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 479.55, ALogP 4.55, HBA 6, HBD 1, PSA 84.66, QED 0.56
Compound (SMILES): CCn1nc(-c2ccc([C@H](C)N3CC[C@](CC(C)(C)O)(c4ccccc4)OC3=O)cc2)ccc1=O
InChIKey: FLPLVVYBPARPKW-MMTVBGGISA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 = 46300 nM (pChEMBL 4.329999923706055)
Descriptors: MW 475.59, ALogP 4.89, HBA 6, HBD 1, PSA 84.66, QED 0.53
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(CC(F)(F)F)n2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: CXOMREQXULTUTB-PPHZAIPVSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 = 18900 nM (pChEMBL 4.71999979019165)
Descriptors: MW 529.56, ALogP 5.43, HBA 6, HBD 1, PSA 84.66, QED 0.44
Compound (SMILES): Cc1cc(-c2ccc([C@H](C)N3CC[C@](CC(C)(C)O)(c4ccccc4)OC3=O)cc2)nn(C)c1=O
InChIKey: CMRQSUMZGCSHON-MMTVBGGISA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 475.59, ALogP 4.72, HBA 6, HBD 1, PSA 84.66, QED 0.56
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(CC3CC3)n2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: IYVALPSKVAMDMH-JRPXNJEYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 501.63, ALogP 5.28, HBA 6, HBD 1, PSA 84.66, QED 0.45
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C3CC3)n2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: GDEYVKYYDNYXSM-WRONEBCDSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 = 13100 nM (pChEMBL 4.880000114440918)
Descriptors: MW 487.6, ALogP 5.21, HBA 6, HBD 1, PSA 84.66, QED 0.49
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(F)cc2F)cc1)N1CC[C@](CC(C)(C)O)(c2ccc(F)cc2)OC1=O
InChIKey: ZTMCZWXIGPCMLA-JMQGSBJISA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 = 8600 nM (pChEMBL 5.070000171661377)
Descriptors: MW 483.53, ALogP 6.73, HBA 3, HBD 1, PSA 49.77, QED 0.42
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(F)cc2)cc1)N1CC[C@](CCC(N)=O)(c2ccccc2)OC1=O
InChIKey: IEUDNQIKLSMAIA-UZTOHYMASA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 9: The inhibition of recombinant CYP2C9 by compounds of the invention was measured using a commercial kit from Invitrogen (cat #2859).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 446.52, ALogP 5.56, HBA 3, HBD 1, PSA 72.63, QED 0.52
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(F)cc2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: QBTXWKOWTNTLRJ-MMTVBGGISA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 = 9500 nM (pChEMBL 5.019999980926514)
Descriptors: MW 447.55, ALogP 6.45, HBA 3, HBD 1, PSA 49.77, QED 0.47
Compound (SMILES): C[C@@H](c1ccc(Br)cc1)N1CC[C@](CC(C)(C)O)(c2ccc(F)cc2)OC1=O
InChIKey: PCUYRJPAAXXRSG-NYHFZMIOSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Biological Assay Example 6: The assay was based on a method published by Moody et al. (Xenobiotica 1999). The inhibition of cytochrome P450 3A4-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Erythromycin by the test compound was assayed at 37° C with human recombinant cytochrome P450 3A4.
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 450.35, ALogP 5.55, HBA 3, HBD 1, PSA 49.77, QED 0.65
Compound (SMILES): C[C@@H](c1ccc(OC(F)F)cc1)N1CC[C@](CCO)(c2ccc(F)cc2)OC1=O
InChIKey: OALZCBAIPRRJJG-QKKBWIMNSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 9: The inhibition of recombinant CYP2C9 by compounds of the invention was measured using a commercial kit from Invitrogen (cat #2859).
Measurement: IC50 = 24600 nM (pChEMBL 4.610000133514404)
Descriptors: MW 409.4, ALogP 4.61, HBA 4, HBD 1, PSA 59, QED 0.73
Compound (SMILES): C[C@@H](c1ccc(Br)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: DNGAQKDEHIEQAQ-AOMKIAJQSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 9: The inhibition of recombinant CYP2C9 by compounds of the invention was measured using a commercial kit from Invitrogen (cat #2859).
Measurement: IC50 = 9500 nM (pChEMBL 5.019999980926514)
Descriptors: MW 432.36, ALogP 5.41, HBA 3, HBD 1, PSA 49.77, QED 0.69
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)n2)cc1)N1CC[C@](CCCO)(c2ccccc2)OC1=O
InChIKey: PGQZLXAQNFHWTD-AFMDSPMNSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 447.54, ALogP 4.02, HBA 6, HBD 1, PSA 84.66, QED 0.59
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(=O)(=O)C3CC3)cc2)ncc1C(F)(F)F
InChIKey: BAOWDLOLYGOWOE-GHMZBOCLSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 431.44, ALogP 3.32, HBA 7, HBD 2, PSA 101.41, QED 0.69
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(C)(=O)=O)cc2)ncc1C(F)(F)F
InChIKey: JLMIHNJHBAEFKC-NXEZZACHSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 405.4, ALogP 2.79, HBA 7, HBD 2, PSA 101.41, QED 0.76
Compound (SMILES): C[C@@H](Oc1nc(Nc2ccc(S(C)(=O)=O)cc2)ncc1C(F)(F)F)C(C)(C)O
InChIKey: PAEDTQQTYBULPN-SNVBAGLBSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 419.43, ALogP 3.18, HBA 7, HBD 2, PSA 101.41, QED 0.74
Compound (SMILES): O=c1[nH]nc2c3c(cccc13)N=C(CN1Cc3ccccc3C1)N2
InChIKey: JLFSBHQQXIAQEC-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Mus musculus
UniProt: O88554
Assay: Inhibition of mouse recombinant PARP2
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 317.35, ALogP 2.39, HBA 5, HBD 2, PSA 73.38, QED 0.76
Compound (SMILES): CCc1cc(O)c(F)cc1-c1ccc2c(-c3nc4c([nH]3)CCN(C(=O)c3ccc(F)cc3)C4)n[nH]c2c1
InChIKey: SYMXGYXFLGDULR-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of Tyk2 (unknown origin) using peptide substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by microfluidic assay
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 499.52, ALogP 5.36, HBA 4, HBD 3, PSA 97.9, QED 0.31
Compound (SMILES): CCc1cc(O)c(F)cc1-c1ccc2c(-c3nc4c([nH]3)CCN(C(=O)c3cnc(N5CCCCC5)cn3)C4)n[nH]c2c1
InChIKey: XDJGNPSZQSWJCV-UHFFFAOYSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK2/TYK2 in human whole blood lymphocytes assessed as inhibition of IL-23 induced STAT3 phosphorylation preincubated for 45 mins followed by IL23 addition and measured after 20 mins by flow cytometric analysis
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 566.64, ALogP 5.01, HBA 7, HBD 3, PSA 126.92, QED 0.27
Compound (SMILES): COCC(=O)N1CCN(c2ccc(Nc3ncc(C(N)=O)c(NC4CC4)n3)cc2)CC1
InChIKey: AKRODORBCFIPKJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Binding Assay: ATP-site dependent competition binding assay using Ambit KinomeScan Screening kit.
Measurement: Kd = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 425.49, ALogP 1.19, HBA 8, HBD 3, PSA 125.71, QED 0.58
Compound (SMILES): CS(=O)(=O)N1CCN(c2ccc(Nc3ncc(C(N)=O)c(NC4CC4)n3)cc2)CC1
InChIKey: PFDUPXGEXSITJW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Binding Assay: ATP-site dependent competition binding assay using Ambit KinomeScan Screening kit.
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 431.52, ALogP 0.97, HBA 8, HBD 3, PSA 133.55, QED 0.59
Compound (SMILES): NC(=O)c1cnc(Nc2ccc(N3CCC[C@@H](C(N)=O)C3)cc2)nc1NC1CC1
InChIKey: UNRTWZKXADNVLM-GFCCVEGCSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Binding Assay: ATP-site dependent competition binding assay using Ambit KinomeScan Screening kit.
Measurement: Kd = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 395.47, ALogP 1.6, HBA 7, HBD 4, PSA 139.26, QED 0.56
Compound (SMILES): CCOC(=O)/C=C/c1c(OC)ccc2cc(-c3cccc(OC)c3)ccc12
InChIKey: WCLQUDCFQAVYPS-ACCUITESSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14061
Assay: Radioactivity Assay: The determination of IC50 values was performed with enzyme isolated from human placenta (Luu-The, V. et al., J. Steroid Biochem. Mol. Biol., 55:581-587 (1995): Sam, K. M. et al., Drug Des Discov., 15:157-180 (1997)). The radioactivity is determined by means of scintillation measurement.
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 362.43, ALogP 5.1, HBA 4, HBD 0, PSA 44.76, QED 0.45
Compound (SMILES): O=C(O)CCC(=O)Nc1ccc(-c2c(O)ccc3cc(-c4cccc(O)c4)ccc23)cc1
InChIKey: ZTMKPXUZAMIYCW-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14061
Assay: Radioactivity Assay: The determination of IC50 values was performed with enzyme isolated from human placenta (Luu-The, V. et al., J. Steroid Biochem. Mol. Biol., 55:581-587 (1995): Sam, K. M. et al., Drug Des Discov., 15:157-180 (1997)). The radioactivity is determined by means of scintillation measurement.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 427.46, ALogP 5.39, HBA 4, HBD 4, PSA 106.86, QED 0.33
Compound (SMILES): CNC(=O)/C=C/c1cc(OC)cc(-c2ccc3cc(OC)ccc3c2)c1
InChIKey: VIZKFHFQFJRUES-RUDMXATFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: Inhibition assay using P450 CYP enzymes.
Measurement: IC50 = 2250 nM (pChEMBL 5.650000095367432)
Descriptors: MW 347.41, ALogP 4.28, HBA 3, HBD 1, PSA 47.56, QED 0.7
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(F)cc2F)cc1)N1CC[C@](CC(C)(C)O)(c2ccc(F)cc2)OC1=O
InChIKey: ZTMCZWXIGPCMLA-JMQGSBJISA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 9: The inhibition of recombinant CYP2C9 by compounds of the invention was measured using a commercial kit from Invitrogen (cat #2859).
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 483.53, ALogP 6.73, HBA 3, HBD 1, PSA 49.77, QED 0.42
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(F)cc2)cc1)N1CC[C@](CCC(N)=O)(c2ccccc2)OC1=O
InChIKey: IEUDNQIKLSMAIA-UZTOHYMASA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Scintillation Proximity Assay: The inhibition of a microsomal preparation of 11β-HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format.
Measurement: IC50 = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 446.52, ALogP 5.56, HBA 3, HBD 1, PSA 72.63, QED 0.52
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(F)cc2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: QBTXWKOWTNTLRJ-MMTVBGGISA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Biological Assay Example 8: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C19-isoenzyme catalysed N-demethylation of [N-methyl-14C]-Diazepam by the test compound was assayed at 37Â° C. with human recombinant cytochrome P450 2C19.
Measurement: IC50 = 10100 nM (pChEMBL 5)
Descriptors: MW 447.55, ALogP 6.45, HBA 3, HBD 1, PSA 49.77, QED 0.47