lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(CCNc2nc(-c3ncncc3F)cc(=O)n2C)cc1OC
InChIKey: YLMQKVFDDXTWFZ-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Bos taurus
UniProt: P29172
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM beta-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 ug/ml P-GS1, 41.7 uM [gamma-32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25 C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 75.3 nM (pChEMBL 7.119999885559082)
Descriptors: MW 385.4, ALogP 2.05, HBA 8, HBD 1, PSA 91.16, QED 0.67
Compound (SMILES): Cn1c(NCC(=O)c2ccc(Cl)cc2)nc(-c2ncncc2F)cc1=O
InChIKey: GGKJVEBAZKAPHN-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Bos taurus
UniProt: P29172
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM beta-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 ug/ml P-GS1, 41.7 uM [gamma-32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25 C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 607.9 nM (pChEMBL 6.21999979019165)
Descriptors: MW 373.77, ALogP 2.32, HBA 7, HBD 1, PSA 89.77, QED 0.69
Compound (SMILES): CN(CCc1ccc([N+](=O)[O-])cc1)c1nc(-c2ncncc2F)cc(=O)n1C
InChIKey: BIHANFBBEUOMIP-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Bos taurus
UniProt: P29172
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM beta-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 ug/ml P-GS1, 41.7 uM [gamma-32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25 C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 164.8 nM (pChEMBL 6.78000020980835)
Descriptors: MW 384.37, ALogP 1.96, HBA 8, HBD 0, PSA 107.05, QED 0.47
Compound (SMILES): Cc1nc(-c2ccc([C@H]3CN(c4nc(-c5ccncn5)c(O)c(=O)n4C)CCO3)cc2)no1
InChIKey: VMCWQYUFJHULPC-QGZVFWFLSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Bos taurus
UniProt: P29172
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM beta-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 ug/ml P-GS1, 41.7 uM [gamma-32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25 C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 447.46, ALogP 1.88, HBA 11, HBD 1, PSA 132.29, QED 0.49
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)Nc5ccc(N6CCCCC6)nc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: NEQDCWFWVYOBKX-HHDOLNPSSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 14700 nM (pChEMBL 4.829999923706055)
Descriptors: MW 795.95, ALogP 5.26, HBA 9, HBD 3, PSA 146.59, QED 0.15
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(NC(=O)Nc6ccc(OC)nc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: SCCIUWBTSOHVEK-VYQNARHWSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 833.95, ALogP 6.34, HBA 9, HBD 4, PSA 164.61, QED 0.1
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(NC(=O)Nc6ccccc6)nc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: YIZDDSJUVVICBC-WCAWKSPSSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 803.92, ALogP 6.33, HBA 8, HBD 4, PSA 155.38, QED 0.11
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)N6CCSCC6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: YEYJQOPIRCXAMH-ZAQUEYBZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 1760 nM (pChEMBL 5.75)
Descriptors: MW 797.98, ALogP 5.48, HBA 8, HBD 2, PSA 121.67, QED 0.18
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6ccc(N7CCN(C(C)=O)CC7)cc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: CJSPFBXNXWDZGH-CRKOEVGVSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 914.08, ALogP 6.21, HBA 9, HBD 3, PSA 154.01, QED 0.12
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6ccc(N7CCN(C)CC7)cc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ZNEQYXFNVWWCOJ-MVRBIKRMSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 7040 nM (pChEMBL 5.150000095367432)
Descriptors: MW 886.07, ALogP 6.29, HBA 9, HBD 3, PSA 136.94, QED 0.12
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6ccc(N7CCOCC7)nc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ALUBYALCOZFVQB-QCDYIZFSSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 874.02, ALogP 5.77, HBA 10, HBD 3, PSA 155.82, QED 0.13
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5cccc(C(=O)Nc6ccccc6)c5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ZUEWAKQVCILIJO-COCZKOEFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 2130 nM (pChEMBL 5.670000076293945)
Descriptors: MW 787.92, ALogP 6.54, HBA 7, HBD 3, PSA 130.46, QED 0.13
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6cccc(C(N)=O)c6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: HMVQIFYVRUUARJ-COCZKOEFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 15970 nM (pChEMBL 4.800000190734863)
Descriptors: MW 830.95, ALogP 5.64, HBA 8, HBD 4, PSA 173.55, QED 0.12
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6cccc(O)c6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ZGSOWIAWZLPMBJ-COCZKOEFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 8070 nM (pChEMBL 5.090000152587891)
Descriptors: MW 803.92, ALogP 6.25, HBA 8, HBD 4, PSA 150.69, QED 0.11
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6ccccc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ZRSYWCIWUUCJFJ-COCZKOEFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 7630 nM (pChEMBL 5.119999885559082)
Descriptors: MW 787.92, ALogP 6.54, HBA 7, HBD 3, PSA 130.46, QED 0.13
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6ccc(N)cc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ACZMHYDTZOAQBH-COCZKOEFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 2420 nM (pChEMBL 5.619999885559082)
Descriptors: MW 802.94, ALogP 6.12, HBA 8, HBD 4, PSA 156.48, QED 0.09
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6cccc(OCc7ccccc7)c6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: MGPNHBYVGAWOLH-GTMCEHENSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 17200 nM (pChEMBL 4.760000228881836)
Descriptors: MW 894.04, ALogP 8.12, HBA 8, HBD 3, PSA 139.69, QED 0.09
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6cccc(OC)c6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: WJLYZJUAZGDOJF-MJPWBCPGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 6530 nM (pChEMBL 5.179999828338623)
Descriptors: MW 817.95, ALogP 6.55, HBA 8, HBD 3, PSA 139.69, QED 0.12
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6ccc(OC)cc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ZGYCWFMKMMGTNI-MJPWBCPGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 19500 nM (pChEMBL 4.710000038146973)
Descriptors: MW 817.95, ALogP 6.55, HBA 8, HBD 3, PSA 139.69, QED 0.12
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6ccc(OCCCC)cc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: CELMLYCAIZGNJJ-ZYBCLOSLSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 860.03, ALogP 7.72, HBA 8, HBD 3, PSA 139.69, QED 0.07
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5cccc(C(=O)Nc6ccc(N7CCN(c8ccc(OC)cc8)CC7)cc6)c5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: MPARRWFWOOSGFT-BNLBYEDMSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 978.17, ALogP 7.88, HBA 10, HBD 3, PSA 146.17, QED 0.09
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)Nc6cccc(OC(C)C)c6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: IUKGTWNYPLJBGP-GSVOJQHPSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 13700 nM (pChEMBL 4.860000133514404)
Descriptors: MW 846, ALogP 7.33, HBA 8, HBD 3, PSA 139.69, QED 0.1
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)NC6CCC(NC(=O)OC(C)(C)C)CC6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ITYPOIOJLXUMJH-KWMOVAKFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 909.1, ALogP 6.85, HBA 9, HBD 4, PSA 168.79, QED 0.1
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)NNC(C)(C)C)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: WUQQGTBJNNXQJA-YDAXCOIMSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 3410 nM (pChEMBL 5.46999979019165)
Descriptors: MW 782.95, ALogP 5.32, HBA 8, HBD 4, PSA 142.49, QED 0.11
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)NN6CCN(c7ccccn7)CC6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ORURZZOCXOQQIN-QCDYIZFSSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 873.03, ALogP 5.15, HBA 10, HBD 3, PSA 149.83, QED 0.14
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)NN6CCN(C)CC6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: DWHDFUVHGLXNKO-YATWDLPUSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 2510 nM (pChEMBL 5.599999904632568)
Descriptors: MW 809.97, ALogP 4.18, HBA 9, HBD 3, PSA 136.94, QED 0.17
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(NC(=O)c6ccccc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: OTFUCMLNWGKDEZ-COCZKOEFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 787.92, ALogP 6.54, HBA 7, HBD 3, PSA 130.46, QED 0.13
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(NC(=O)c6ccc(OC)cc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ISLCCZIUPKFGKN-MJPWBCPGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 817.95, ALogP 6.55, HBA 8, HBD 3, PSA 139.69, QED 0.12
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(NC(=O)c6ccc(N)cc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: IZKQXLOXCDKRSU-COCZKOEFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 802.94, ALogP 6.12, HBA 8, HBD 4, PSA 156.48, QED 0.09
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(NC(=O)c6ccc(N(C)C)cc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: NOOTYVQYKTUNKR-CXNSMIOJSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 830.99, ALogP 6.61, HBA 8, HBD 3, PSA 133.7, QED 0.12
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(NC(=O)CCCCCCC)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: KUEBPEWAUJGQRQ-YMJVKMAGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 21700 nM (pChEMBL 4.659999847412109)
Descriptors: MW 810.01, ALogP 7.59, HBA 7, HBD 3, PSA 130.46, QED 0.07
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(NC(=O)c6ccc(CN(CC)CC)cc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ATRYSYOKKNIJSL-MVRBIKRMSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 2260 nM (pChEMBL 5.650000095367432)
Descriptors: MW 873.07, ALogP 7.38, HBA 8, HBD 3, PSA 133.7, QED 0.09
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(NC(=O)c6ccc(NC)cc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: FCBOHKLIJSVJMO-MJPWBCPGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 816.96, ALogP 6.58, HBA 8, HBD 4, PSA 142.49, QED 0.1
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(NC(=O)c6ccc(N(CC)CC)cc6)cc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: PWOQCDXDGLGZLQ-ZYBCLOSLSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 859.04, ALogP 7.39, HBA 8, HBD 3, PSA 133.7, QED 0.1
Compound (SMILES): Cc1c(C)n(Cc2ccc(-c3ccccc3C(=O)O)cc2)c2ccc(C(=O)N[C@@H](C)c3cccc(OC(C)C)c3)cc12
InChIKey: UAYKPDKWEPQCKH-DEOSSOPVSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Lanthascreen Competitive Binding Assay: The assay was performed according to manufacturer protocol. A mixture of nM GST-PPARG-LBD, 5 nM Tb-GST-antibody, 5 nM Fluormone Pan-PPAR Green, and serial dilutions of the experimental compound, beginning at 10 μM downwards, was added to wells of black 384-well low-volume plates (Greiner) to a total volume of 18 μL. All dilutions were made in TR-FRET assay buffer C. DMSO at 2% final concentration was used as a no-ligand control. Experiment was performed in triplicate, and incubated for 2 hours in the dark prior to assay read in Perkin Elmer ViewLux ultra HTS microplate reader. FRET signal was measured by excitation at 340 nm and emission at 520 nm for fluorescein and 490 nm for terbium. Fold change over DMSO was calculated using GraphPad Prism Software (La Jolla, Calif.) by calculating 520 nm/490 nm ratio. Graphs were plotted as fold change of FRET signal for compound treatment over DMSO-only control.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 560.69, ALogP 7.95, HBA 4, HBD 2, PSA 80.56, QED 0.19