lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(NC(=O)NC6CCN(C)CC6)nc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: SJDMIRPKIHYUCM-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 = 2920 nM (pChEMBL 5.539999961853027)
Descriptors: MW 824.99, ALogP 4.9, HBA 9, HBD 4, PSA 158.62, QED 0.14
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(-c5ccc(C(=O)N(C)C)o5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: QMNHISFQHZSZCX-JUKUECOXSA-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 = 3420 nM (pChEMBL 5.46999979019165)
Descriptors: MW 729.84, ALogP 4.58, HBA 8, HBD 2, PSA 134.81, QED 0.2
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCOCC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: XJCPULIHXFIZOP-HEVIKAOCSA-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 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 705.82, ALogP 3.09, HBA 8, HBD 2, PSA 130.9, QED 0.26
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(C)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: VINDQDYEPNHNKQ-PXLJZGITSA-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 = 12200 nM (pChEMBL 4.909999847412109)
Descriptors: MW 718.86, ALogP 3.01, HBA 8, HBD 2, PSA 124.91, QED 0.26
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(CC)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: GAARYPFMGZTUSF-ZPGRZCPFSA-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 = 8040 nM (pChEMBL 5.090000152587891)
Descriptors: MW 732.89, ALogP 3.4, HBA 8, HBD 2, PSA 124.91, QED 0.24
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(C(C)C)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: JUKYJTSFENURII-BCRBLDSWSA-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 = 2240 nM (pChEMBL 5.650000095367432)
Descriptors: MW 746.91, ALogP 3.79, HBA 8, HBD 2, PSA 124.91, QED 0.24
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(CCO)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: BGZVJJCLWJQDPD-ZPGRZCPFSA-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 = 6820 nM (pChEMBL 5.170000076293945)
Descriptors: MW 748.88, ALogP 2.37, HBA 9, HBD 3, PSA 145.14, QED 0.2
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(CCOC)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: OCZUEDNFZLWPEY-BCRBLDSWSA-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 = 9120 nM (pChEMBL 5.039999961853027)
Descriptors: MW 762.91, ALogP 3.02, HBA 9, HBD 2, PSA 134.14, QED 0.21
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(CCCO)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: FYYNKEATFHKTBH-BCRBLDSWSA-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 = 11300 nM (pChEMBL 4.949999809265137)
Descriptors: MW 762.91, ALogP 2.76, HBA 9, HBD 3, PSA 145.14, QED 0.19
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(CCCCO)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: MIHDVZBMEYHLOS-UWXQCODUSA-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 = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 776.94, ALogP 3.15, HBA 9, HBD 3, PSA 145.14, QED 0.14
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(CCCN(C)C)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: AVNPLQIOVHQFAT-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 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 789.98, ALogP 3.33, HBA 9, HBD 2, PSA 128.15, QED 0.2
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(C(C)=O)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: MONWIUSEFBOZFB-ZPGRZCPFSA-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 = 10900 nM (pChEMBL 4.960000038146973)
Descriptors: MW 746.87, ALogP 2.92, HBA 8, HBD 2, PSA 141.98, QED 0.25
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(S(C)(=O)=O)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: GWPBPJXIAURZGV-PXLJZGITSA-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 = 11200 nM (pChEMBL 4.949999809265137)
Descriptors: MW 782.92, ALogP 2.34, HBA 9, HBD 2, PSA 159.05, QED 0.23
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(S(=O)(=O)CC)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: MMEGHIZPLVCKKK-ZPGRZCPFSA-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 = 2820 nM (pChEMBL 5.550000190734863)
Descriptors: MW 796.95, ALogP 2.73, HBA 9, HBD 2, PSA 159.05, QED 0.22
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCC(N6CCN(C)CC6)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: IOZXECSGCQCHGF-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 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 801.99, ALogP 3.47, HBA 9, HBD 2, PSA 128.15, QED 0.23
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(CC6CCCC6)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: QHSQTDUGXXBHGV-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 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 786.98, ALogP 4.57, HBA 8, HBD 2, PSA 124.91, QED 0.21
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(CC6CCNCC6)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: QHRIPYHARJRXIH-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 = 8170 nM (pChEMBL 5.090000152587891)
Descriptors: MW 801.99, ALogP 3.38, HBA 9, HBD 3, PSA 136.94, QED 0.2
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(CCN6CCCCC6)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: UDYNSGNOZYBHLA-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 = 5530 nM (pChEMBL 5.260000228881836)
Descriptors: MW 816.02, ALogP 3.86, HBA 9, HBD 2, PSA 128.15, QED 0.21
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN(CCN6CCOCC6)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: WQKONMWIFWSSSD-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 = 6090 nM (pChEMBL 5.210000038146973)
Descriptors: MW 817.99, ALogP 2.71, HBA 10, HBD 2, PSA 137.38, QED 0.21
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)NN5CCN(c6ccccn6)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: REGJPCAIWDVDNX-QARUCVQPSA-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 = 2480 nM (pChEMBL 5.610000133514404)
Descriptors: MW 796.93, ALogP 3.48, HBA 10, HBD 3, PSA 149.83, QED 0.17
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCCN(C)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: VSHMJRDIOFZVNT-ZPGRZCPFSA-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 = 3630 nM (pChEMBL 5.440000057220459)
Descriptors: MW 732.89, ALogP 3.4, HBA 8, HBD 2, PSA 124.91, QED 0.25
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN6CCCC6C5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: NUBFJAZVCPPPLP-HNNLUAMWSA-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 = 6600 nM (pChEMBL 5.179999828338623)
Descriptors: MW 744.9, ALogP 3.54, HBA 8, HBD 2, PSA 124.91, QED 0.25
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN6CCN(C(C)=O)CC6C5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: GLDNZQYGNSOWKA-HWHSMDOUSA-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 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 801.95, ALogP 2.61, HBA 9, HBD 2, PSA 145.22, QED 0.25
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN6CCN(CC(C)C)CC6C5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: MIPWODRTRBZYNE-MJPQJCIXSA-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 = 3980 nM (pChEMBL 5.400000095367432)
Descriptors: MW 816.02, ALogP 3.72, HBA 9, HBD 2, PSA 128.15, QED 0.22
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN6CCN(C(=O)OC(C)(C)C)CC6C5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: SPNMGKKKLSOOCQ-SAGRBAIFSA-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 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 860.03, ALogP 4, HBA 10, HBD 2, PSA 154.45, QED 0.24
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN6CCN(C=O)CC6C5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: BAZGKZBDGLGUSD-UCFJPLQUSA-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 = 12100 nM (pChEMBL 4.920000076293945)
Descriptors: MW 787.92, ALogP 2.22, HBA 9, HBD 2, PSA 145.22, QED 0.18
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCN6CCN(CC)CC6C5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: LZMJCQWNDIGSIP-HWHSMDOUSA-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 = 5040 nM (pChEMBL 5.300000190734863)
Descriptors: MW 787.97, ALogP 3.08, HBA 9, HBD 2, PSA 128.15, QED 0.24
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCC(O)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: ASYDBVRDAOJREX-PXLJZGITSA-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 = 10700 nM (pChEMBL 4.96999979019165)
Descriptors: MW 719.84, ALogP 3.22, HBA 8, HBD 3, PSA 141.9, QED 0.23
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCC(OC)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: POYVJUSYLIGQCQ-ZPGRZCPFSA-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 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 733.87, ALogP 3.87, HBA 8, HBD 2, PSA 130.9, QED 0.24
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCC(C(=O)OCC)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: JZAVQNHDPXFZNV-BCRBLDSWSA-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 = 3860 nM (pChEMBL 5.409999847412109)
Descriptors: MW 775.91, ALogP 4.04, HBA 9, HBD 2, PSA 147.97, QED 0.17
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCC(C(=O)N(C)CCN(C)C)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: OBYFMRYTDUFAQC-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 = 4970 nM (pChEMBL 5.300000190734863)
Descriptors: MW 832.02, ALogP 3.49, HBA 9, HBD 2, PSA 145.22, QED 0.2
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCC(NC(=O)CCO)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: UOSYPEJGZRITSC-BAEGBANDSA-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 = 7650 nM (pChEMBL 5.119999885559082)
Descriptors: MW 790.92, ALogP 2.72, HBA 9, HBD 4, PSA 171, QED 0.16
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCC(NC(=O)c6ccc(N(C)C)cc6)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: YYVFUVDTBBIBHS-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 866.04, ALogP 4.72, HBA 9, HBD 3, PSA 154.01, QED 0.15
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCC(NC(=O)c6ccc(N7CCN(C)CC7)cc6)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: YRIWHMGNXZETGH-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 = 6020 nM (pChEMBL 5.21999979019165)
Descriptors: MW 921.12, ALogP 4.41, HBA 10, HBD 3, PSA 157.25, QED 0.15
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)N5CCC(N(C)C)CC5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: VQOICHPDWXYAPI-BCRBLDSWSA-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 = 2230 nM (pChEMBL 5.650000095367432)
Descriptors: MW 746.91, ALogP 3.79, HBA 8, HBD 2, PSA 124.91, QED 0.24