lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(Nc1ccnn1-c1ccc(Cl)cc1)c1cnn2cccnc12
InChIKey: SMVZAQMYQIIFKQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 338.76, ALogP 2.82, HBA 6, HBD 1, PSA 77.11, QED 0.62
Compound (SMILES): O=C(Nc1ccncc1-c1cccc(F)c1)c1cnn2cccnc12
InChIKey: OEIOCPLLBAECAL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 333.33, ALogP 3.18, HBA 5, HBD 1, PSA 72.18, QED 0.62
Compound (SMILES): COc1ccc(Cl)cc1-c1c(NC(=O)c2cnn3cccnc23)cnn1CCO
InChIKey: JWMNWMLDJKHWSK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 412.84, ALogP 2.5, HBA 8, HBD 2, PSA 106.57, QED 0.5
Compound (SMILES): COc1cnc(C(F)(F)F)cc1-c1nn(CC(C)(C)O)cc1NC(=O)c1cnn2cccnc12
InChIKey: IJZCGMKRBKNOGJ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 475.43, ALogP 3.04, HBA 9, HBD 2, PSA 119.46, QED 0.44
Compound (SMILES): COc1ccc(C#N)cc1-c1nn(Cc2nncn2C)cc1NC(=O)c1cnn2cccnc12
InChIKey: DNAVEOJHRAGDMN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 454.45, ALogP 1.9, HBA 11, HBD 1, PSA 140.84, QED 0.41
Compound (SMILES): COc1ncc(C#N)cc1-c1n[nH]cc1NC(=O)c1cnn2cccnc12
InChIKey: SEQQCOJLCFZLND-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 6.6 nM (pChEMBL 8.180000305175781)
Descriptors: MW 360.34, ALogP 1.65, HBA 8, HBD 2, PSA 133.88, QED 0.56
Compound (SMILES): COc1ccc(Cl)cc1-c1nc(C)sc1NC(=O)c1cnn2cccnc12
InChIKey: XJIGRSGPENMQAL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 399.86, ALogP 4.08, HBA 7, HBD 1, PSA 81.41, QED 0.56
Compound (SMILES): O=C(Nc1c[nH]nc1-n1cc(Cl)ccc1=O)c1cnn2cccnc12
InChIKey: YDLOXCYXIDDCNZ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 980 nM (pChEMBL 6.010000228881836)
Descriptors: MW 355.75, ALogP 1.51, HBA 7, HBD 2, PSA 109.97, QED 0.58
Compound (SMILES): COc1ccc(Cl)cc1-c1c(NC(=O)c2c(N)nn3cccnc23)cnn1CC(N)=O
InChIKey: NCFRXNQURQEQIZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 440.85, ALogP 1.57, HBA 9, HBD 3, PSA 155.45, QED 0.41
Compound (SMILES): COc1ccc(Cl)cc1-c1nn(CC(=O)N2CCCC2C)cc1NC(=O)c1cnn2cccnc12
InChIKey: HPYAZSADACBSNT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 493.96, ALogP 3.52, HBA 8, HBD 1, PSA 106.65, QED 0.44
Compound (SMILES): COc1ccc(Cl)cc1-c1nn(CC(=O)N2CC=CCC2)cc1NC(=O)c1cnn2cccnc12
InChIKey: BGASWXPPHGCMFI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The activity of the isolated JAK3 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Leu-Pro-Leu-Asp-Lys-Asp-Tyr-Tyr-Val-Val-Arg) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 5 nM purified JAK3 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 5 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 491.94, ALogP 3.3, HBA 8, HBD 1, PSA 106.65, QED 0.41
Compound (SMILES): COc1ccc(C#N)cc1-c1nn(CC2(O)CCCC2)cc1NC(=O)c1cnn2cccnc12
InChIKey: BVMSQKXHZARQEQ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 457.49, ALogP 3.03, HBA 9, HBD 2, PSA 130.36, QED 0.45
Compound (SMILES): COc1ccc(F)cc1-c1nn(CC2(O)CCOCC2)cc1NC(=O)c1cnn2cccnc12
InChIKey: SZOIUXXJQSKBJX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The activity of the isolated JAK3 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Leu-Pro-Leu-Asp-Lys-Asp-Tyr-Tyr-Val-Val-Arg) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 5 nM purified JAK3 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 5 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 710 nM (pChEMBL 6.150000095367432)
Descriptors: MW 466.47, ALogP 2.53, HBA 9, HBD 2, PSA 115.8, QED 0.45
Compound (SMILES): CC1CCCCN1c1nn(CC(C)(C)O)cc1NC(=O)c1cnn2cccnc12
InChIKey: JGERZOWTPSQGTH-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 397.48, ALogP 2.33, HBA 8, HBD 2, PSA 100.58, QED 0.69
Compound (SMILES): N#CC1CCN(c2n[nH]cc2NC(=O)c2cnn3cccnc23)CC1
InChIKey: SDGQVTSJYRDVBO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 176 nM (pChEMBL 6.75)
Descriptors: MW 336.36, ALogP 1.44, HBA 7, HBD 2, PSA 115, QED 0.75
Compound (SMILES): CCOc1ccc(Cl)cc1-c1nn([C@H]2CCCC[C@@H]2O)cc1NC(=O)c1cnn2cccnc12
InChIKey: KYALABLULOMGIM-PMACEKPBSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The activity of the isolated JAK3 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Leu-Pro-Leu-Asp-Lys-Asp-Tyr-Tyr-Val-Val-Arg) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 5 nM purified JAK3 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 5 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 480.96, ALogP 4.37, HBA 8, HBD 2, PSA 106.57, QED 0.42
Compound (SMILES): COc1ccc(Cl)cc1-c1nn(CC(O)(C(F)(F)F)C(F)(F)F)cc1NC(=O)c1cnn2cccnc12
InChIKey: BAJWFUQPOIPLDS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The activity of the isolated JAK3 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Leu-Pro-Leu-Asp-Lys-Asp-Tyr-Tyr-Val-Val-Arg) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 5 nM purified JAK3 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 5 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 548.83, ALogP 4.36, HBA 8, HBD 2, PSA 106.57, QED 0.35
Compound (SMILES): COc1ncc(Cl)cc1-c1nn(CC(=O)N(C)C)cc1NC(=O)c1cnn2cccnc12
InChIKey: ZKIGAFPVFDLLDE-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition Assay: The activity of the isolated JAK1, JAK2 or TYK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr) fluorescently labeled on the N-terminus with 5-carboxyfluorescein using the Caliper LabChip technology (Caliper Life Sciences, Hopkinton, Mass.). To determine the inhibition constants (Ki) of Examples 1-508, compounds were diluted serially in DMSO and added to 50 uL kinase reactions containing 1.5 nM JAK1, 0.2 nM purified JAK2 or 1 nM purified TYK2 enzyme, 100 mM Hepes pH7.2, 0.015% Brij-35, 1.5 uM peptide substrate, 25 uM ATP, 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22Â° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 uL of an EDTA containing solution (100 mM Hepes pH 7.2, 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM.
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 454.88, ALogP 1.99, HBA 9, HBD 1, PSA 119.54, QED 0.47
Compound (SMILES): CSc1cccc(NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccc(Br)s2)c1
InChIKey: GGCRLIFVACLEJF-ZDUSSCGKSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: In Vitro Assay: Chinese hamster ovary (CHO) cells expressing the human orexin-1 receptor and the human orexin-2 receptor, respectively, are grown in culture medium (Ham F-12 with L-Glutamine) containing 300 ug/ml G418, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat inactivated fetal calf serum (FCS). The cells are seeded at 20'000 cells/well into 384-well black clear bottom sterile plates (Greiner). The seeded plates are incubated overnight at 37 C. in 5% CO2.Human orexin-A as an agonist is prepared as 1 mM stock solution in MeOH: water (1:1), diluted in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/l and 20 mM HEPES for use in the assay at a final concentration of 3 nM.Antagonists are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates using DMSO followed by a transfer of the dilutions into in HBSS containing 0.1% bovine serum albumin (BSA), NaHCO3: 0.375 g/l and 20 mM HEPES. On the day of the assay, 50 ul of staining buffer.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 461.43, ALogP 4.02, HBA 5, HBD 1, PSA 66.48, QED 0.68
Compound (SMILES): COc1ccc(S(=O)(=O)N2CCC[C@H]2C(=O)Nc2cccc(SC)c2)cc1
InChIKey: DIUDVHGBTFDFCN-SFHVURJKSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 406.53, ALogP 3.21, HBA 5, HBD 1, PSA 75.71, QED 0.75
Compound (SMILES): CC(C)[C@@H](OCCOc1ccccc1)C(=O)N[C@@H](C)c1ccc(C(=O)O)cc1
InChIKey: PTEYRFYBLQUWJP-OXJNMPFZSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: In Vitro Binding Assay: hEP1 and hEP4 membranes are prepared from recombinant HEK293 cells stably expressing the human EP1 (Genbank accession number AY275470) or EP4 (Genbank accession number AY429109) receptors. hEP2 and hEP3 membranes are prepared from HEK293 cells transiently transfected with EP2 (Genbank accession number AY275471) or EP3 (isoform VI: Genbank accession number AY429108) receptor plasmids. Frozen cell pellets are homogenized in homogenization buffer using a Teflon/glass homogenizer. Membrane protein is aliquoted and quick frozen on dry ice prior to storage at -80 C. Homogenization buffer contained 10 mM Tris-HCl, pH 7.4, 250 mM sucrose, 1 mM EDTA, 0.3 mM indomethacin and plus Complete, with EDTA, obtained from Roche Molecular Biochemicals (Catalog Number 1 697 498).Kd values for [3]H-PGE2 binding to each receptor are determined by saturation binding studies or homologous competition. Compounds are tested in a 96-well format using a three-fold dilution series.
Measurement: Ki = 0.45 nM (pChEMBL 9.350000381469727)
Descriptors: MW 385.46, ALogP 3.68, HBA 4, HBD 2, PSA 84.86, QED 0.61
Compound (SMILES): CCC(CC)(Cc1ccc(C(=O)Oc2ccc(C(=N)N)cc2F)s1)C(=O)N[C@@H](CO)C(=O)O
InChIKey: LFSLIAZOFSRRDB-HNNXBMFYSA-N
Target: Serine protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07477
Assay: Inhibition Assay: Using a 96 well plate (#3915, Costar), a test compound (25 μL) was mixed with 20 μM fluorescence enzyme substrate (Boc-Phe-Ser-Arg-AMC, 50 μL) mixed with 200 mM Tris-HCl buffer (pH 8.0), and human trypsin (Sigma, 25 μL) was added. Using a fluorescence plate reader fmax (Molecular Devices, Inc.), the reaction rate was measured from the time-course changes at excitation wavelength 355 nm and fluorescence wavelength 460 nm.
Measurement: Ki = 1.87 nM (pChEMBL 8.729999542236328)
Descriptors: MW 479.53, ALogP 2.3, HBA 7, HBD 5, PSA 162.8, QED 0.14
Compound (SMILES): CCC(CC)(Cc1ccc(C(=O)Oc2ccc(C(=N)N)cc2F)s1)C(=O)N1CCC[C@H]1C(=O)O
InChIKey: PJQIIQDUTSQWIS-KRWDZBQOSA-N
Target: Serine protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07477
Assay: Inhibition Assay: Using a 96 well plate (#3915, Costar), a test compound (25 μL) was mixed with 20 μM fluorescence enzyme substrate (Boc-Phe-Ser-Arg-AMC, 50 μL) mixed with 200 mM Tris-HCl buffer (pH 8.0), and human trypsin (Sigma, 25 μL) was added. Using a fluorescence plate reader fmax (Molecular Devices, Inc.), the reaction rate was measured from the time-course changes at excitation wavelength 355 nm and fluorescence wavelength 460 nm.
Measurement: Ki = 6.38 nM (pChEMBL 8.199999809265137)
Descriptors: MW 489.57, ALogP 3.81, HBA 6, HBD 3, PSA 133.78, QED 0.21
Compound (SMILES): CCC(CC)(Cc1ccc(C(=O)Oc2ccc(C(=N)N)cc2F)s1)C(=O)N[C@@H](CC(=O)O)C(=O)O
InChIKey: IBHPUOCNUKPTBM-HNNXBMFYSA-N
Target: Serine protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07477
Assay: Inhibition Assay: Using a 96 well plate (#3915, Costar), a test compound (25 μL) was mixed with 20 μM fluorescence enzyme substrate (Boc-Phe-Ser-Arg-AMC, 50 μL) mixed with 200 mM Tris-HCl buffer (pH 8.0), and human trypsin (Sigma, 25 μL) was added. Using a fluorescence plate reader fmax (Molecular Devices, Inc.), the reaction rate was measured from the time-course changes at excitation wavelength 355 nm and fluorescence wavelength 460 nm.
Measurement: Ki = 0.82 nM (pChEMBL 9.09000015258789)
Descriptors: MW 507.54, ALogP 2.78, HBA 7, HBD 5, PSA 179.87, QED 0.13
Compound (SMILES): CCC(CC)(Cc1ccc(C(=O)Oc2ccc(C(=N)N)cc2F)s1)C(=O)N[C@@H](CCC(=O)O)C(=O)O
InChIKey: MRDGTXNCJIRKAP-INIZCTEOSA-N
Target: Serine protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07477
Assay: Inhibition Assay: Using a 96 well plate (#3915, Costar), a test compound (25 μL) was mixed with 20 μM fluorescence enzyme substrate (Boc-Phe-Ser-Arg-AMC, 50 μL) mixed with 200 mM Tris-HCl buffer (pH 8.0), and human trypsin (Sigma, 25 μL) was added. Using a fluorescence plate reader fmax (Molecular Devices, Inc.), the reaction rate was measured from the time-course changes at excitation wavelength 355 nm and fluorescence wavelength 460 nm.
Measurement: Ki = 2.01 nM (pChEMBL 8.699999809265137)
Descriptors: MW 521.57, ALogP 3.17, HBA 7, HBD 5, PSA 179.87, QED 0.12
Compound (SMILES): Nc1ncnn2c(C3CCNC3)cc(-c3cc(F)c(CO)c(F)c3)c12
InChIKey: ZCKFOTLMGZMGPU-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Radiometric Assay: ALKl (Invitrogen, Carlsbad, CA, USA) kinase activity was measured at ProQinase GmbH ( Freiburg. Germany) in a radiometric assay using gamma-33P-ATP and casein (Sigma, St. Louis, MO, USA) as substrate in 96-weli PerkinElmer FlashPlates (Boston, MA, USA). The compounds were tested at 10 concentrations in the range of 1 x 10"4 M to 3 x 10"9 M in a total volume of 50 ul with a finalDMSO concentration of 1 % each. The assay components were mixed in the order: 20 ul assay buffer (70 mM HEPES-NaOH, pi I 7.5. 3 mM MgCl2, 3 mM MnCl2, 2uM sodium orthovanadate, 1.2 mM DTT); - 5ul gamma-33P-ATP (1.0ug/50ug in water, approx. 6 x10E+5 cpm per well); 5 ul test compound solution (in 10% DMSO);10 ul substrate (200 ug/ml, 1.0ug/50ml final concentration) / enzyme (4 ug/ml, 20 ng/50ul = 5.5 nM final concentration) solution (1 : 1 mixture).
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 345.35, ALogP 1.83, HBA 6, HBD 3, PSA 88.47, QED 0.67
Compound (SMILES): COc1cc(-c2cc(C(O)C3CC3)n3ncnc(N)c23)ccc1CO
InChIKey: CETAVAHOOHFRIY-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Flashplate Assay: In vitro enzyme inhibition using scintillation of incorporated radio label (flashplate assay). Test compounds diluted in DMSO are mixed with a suitable substrate / co-substrate (here: bio- tinylated a-casein and 3P-ATP) in a corresponding assay buffer. Addition of the enzyme of interest (here: ALKl kinase) starts the enzyme reaction. The enzyme-catalyzed incorporation of radio label into the substrate is measured via scintillation. Incorporated radio label is separated from free radio label via specific binding of the biotinylated substrate to strepavidin-coated microliter plates (flashplates) and concomitant washing steps. The scintillation signal intensity (counts per minutes, cpm) is proportional to the enzyme activity. Enzyme inhibition results in a decreased signal intensity. IC50 values of the test compounds are determined by cpm-versus-[I] plots. Reaction buffer: Reaction buffer contains 50 mM Tris pi I 8.0 (Sigma), 1 mM MnCi2 (Sigma), 0.01% Nonidet P40 (Fluka).
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 340.38, ALogP 1.92, HBA 7, HBD 3, PSA 105.9, QED 0.66
Compound (SMILES): c1ccc2c(-c3cnn4cc(-c5ccc(OCCN6CCOCC6)cc5)cnc34)ccnc2c1
InChIKey: DXLXRNZCYAYUED-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Kinase assays were performed using the assay kit by Reaction Biology Corp (Malvern, Pa.). The compounds were tested at 10 concentrations by 3-fold serial dilutions starting at 30 μM. Staurosporin was used as a control nonspecific kinase inhibitor. In vitro kinase reactions using purified kinases were carried out in the presence of 10 μM ATP and test compounds.
Measurement: IC50 = 2418 nM (pChEMBL 5.619999885559082)
Descriptors: MW 451.53, ALogP 4.32, HBA 7, HBD 0, PSA 64.78, QED 0.38
Compound (SMILES): CN(C)CCCOc1ccc(-c2cnc3c(-c4ccnc5ccccc45)cnn3c2)cc1
InChIKey: MZIQJPGLZXVJCP-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Kinase Assay: Kinase assays were performed using the assay kit by Reaction Biology Corp (Malvern, Pa.). The compounds were tested at 10 concentrations by 3-fold serial dilutions starting at 30 μM. Staurosporin was used as a control nonspecific kinase inhibitor. In vitro kinase reactions using purified kinases were carried out in the presence of 10 μM ATP and test compounds.
Measurement: IC50 = 26.68 nM (pChEMBL 7.570000171661377)
Descriptors: MW 423.52, ALogP 4.94, HBA 6, HBD 0, PSA 55.55, QED 0.35
Compound (SMILES): Cc1c(-c2ccc(C(=O)N3CCC(C)CC3)cc2)c(=O)oc2c(C=O)c(O)ccc12
InChIKey: KMEHDULTIPVUCA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: IRE-1alpha Assay: A fusion protein comprising glutathione S transferase (GST) and human IRE-1α (GST-IRE-1α) obtained from a 500 ml baculovirus-infected insect cell culture can be used to measure IRE-1α activity in vitro. Five μl of a reaction mixture comprising 1× reaction buffer (5× reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water is added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution are added to test wells. Three μl of a 128 ng/ml IRE-1α preparation are added to each test well and to positive control wells (final concentration 5.82 ng/well). Negative control wells contain only reaction mixture and test compound. After spinning the plates at 1200 rpm for 30 seconds, 3 μl of an IRE-1α human mini-XBP-1 mRNA stem-loop substrate 5'-CAGUCCGCAGCACUG-3' (SEQ ID NO:1), labeled with the fluorescent dye Cy5 at the 5' end and Black Hole Quencher 2 (BH2) at the 3' end, are added to each well of a control plate. The plates are again spun at 1200 rpm for 30 seconds. Final concentrations for the assay are: 63 nM IRE-1α substrate, 5.82 ng IRE-1α protein, and 2.5 μM test compound. The plates are covered with lids and incubated for one hour at 30° C. The plates are then transferred to an ACQUEST™ microplate reader. Data is analyzed using data analysis software, and the percent activity of IRE-1α is calculated.
Measurement: EC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 405.45, ALogP 4.16, HBA 5, HBD 1, PSA 87.82, QED 0.52
Compound (SMILES): Cc1c(-c2ccc(C(=O)N3CCOCC3)cc2)c(=O)oc2c(C=O)c(O)c(Cl)cc12
InChIKey: PBSVVZPAPIKLTK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: IRE-1alpha Assay: A fusion protein comprising glutathione S transferase (GST) and human IRE-1α (GST-IRE-1α) obtained from a 500 ml baculovirus-infected insect cell culture can be used to measure IRE-1α activity in vitro. Five μl of a reaction mixture comprising 1× reaction buffer (5× reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water is added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution are added to test wells. Three μl of a 128 ng/ml IRE-1α preparation are added to each test well and to positive control wells (final concentration 5.82 ng/well). Negative control wells contain only reaction mixture and test compound. After spinning the plates at 1200 rpm for 30 seconds, 3 μl of an IRE-1α human mini-XBP-1 mRNA stem-loop substrate 5'-CAGUCCGCAGCACUG-3' (SEQ ID NO:1), labeled with the fluorescent dye Cy5 at the 5' end and Black Hole Quencher 2 (BH2) at the 3' end, are added to each well of a control plate. The plates are again spun at 1200 rpm for 30 seconds. Final concentrations for the assay are: 63 nM IRE-1α substrate, 5.82 ng IRE-1α protein, and 2.5 μM test compound. The plates are covered with lids and incubated for one hour at 30° C. The plates are then transferred to an ACQUEST™ microplate reader. Data is analyzed using data analysis software, and the percent activity of IRE-1α is calculated.
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 427.84, ALogP 3.41, HBA 6, HBD 1, PSA 97.05, QED 0.51
Compound (SMILES): COc1cc2c(C)c(CC(=O)N3CCOCC3)c(=O)oc2c(C=O)c1O
InChIKey: IFDGMRMUJYGWQQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: IRE-1alpha Assay: A fusion protein comprising glutathione S transferase (GST) and human IRE-1α (GST-IRE-1α) obtained from a 500 ml baculovirus-infected insect cell culture can be used to measure IRE-1α activity in vitro. Five μl of a reaction mixture comprising 1× reaction buffer (5× reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water is added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution are added to test wells. Three μl of a 128 ng/ml IRE-1α preparation are added to each test well and to positive control wells (final concentration 5.82 ng/well). Negative control wells contain only reaction mixture and test compound. After spinning the plates at 1200 rpm for 30 seconds, 3 μl of an IRE-1α human mini-XBP-1 mRNA stem-loop substrate 5'-CAGUCCGCAGCACUG-3' (SEQ ID NO:1), labeled with the fluorescent dye Cy5 at the 5' end and Black Hole Quencher 2 (BH2) at the 3' end, are added to each well of a control plate. The plates are again spun at 1200 rpm for 30 seconds. Final concentrations for the assay are: 63 nM IRE-1α substrate, 5.82 ng IRE-1α protein, and 2.5 μM test compound. The plates are covered with lids and incubated for one hour at 30° C. The plates are then transferred to an ACQUEST™ microplate reader. Data is analyzed using data analysis software, and the percent activity of IRE-1α is calculated.
Measurement: EC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 361.35, ALogP 1.03, HBA 7, HBD 1, PSA 106.28, QED 0.64
Compound (SMILES): Cn1cnc(S(=O)(=O)NCCOc2ccc3c(c2)C(Cc2ccccc2)C(N2CCCC2)CC3)c1
InChIKey: QTUXMVZZQMHBAN-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent glycine transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48067
Assay: Radioligand Binding Assay: Radioligand binding to human GlyT1c transporter-expressing membranes was carried out as described in Mezler et al., Molecular Pharmacology 74:1705-1715, 2008.
Measurement: Ki < 100 nM (pChEMBL 7)
Descriptors: MW 494.66, ALogP 3.51, HBA 6, HBD 1, PSA 76.46, QED 0.46
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCNCC3)cc12
InChIKey: BHDZLFHFYYIDMB-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 323.37, ALogP 3.75, HBA 3, HBD 2, PSA 49.94, QED 0.77
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN(C(=O)CO)CC3)cc12
InChIKey: NAWNCEFBLJLRNH-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 381.41, ALogP 2.99, HBA 4, HBD 2, PSA 78.45, QED 0.73
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN(S(C)(=O)=O)CC3)cc12
InChIKey: SRPJBGDXQQBRRD-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human A-431 cells assessed as reduction in RNA polymerase2 phosphorylation at C-terminal ser2 residue incubated for 4 hrs by In-cell Western analysis
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 401.46, ALogP 3.43, HBA 4, HBD 1, PSA 75.29, QED 0.73
Compound (SMILES): CN1CCC(c2cc3c(-c4cccc(N(C)CCc5ccccc5)n4)ccnc3[nH]2)CC1
InChIKey: RVYGOLVPRWYBBS-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 425.58, ALogP 5.11, HBA 4, HBD 1, PSA 48.05, QED 0.47
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN(CC(O)CO)CC3)cc12
InChIKey: NDLAFOKSJSLKGG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin) by LANCE ULight TR-FRET assay
Measurement: IC50 = 1360 nM (pChEMBL 5.869999885559082)
Descriptors: MW 397.45, ALogP 2.82, HBA 5, HBD 3, PSA 81.61, QED 0.6
Compound (SMILES): CNC(=O)N1CC=C(c2cc3c(-c4cc(F)ccc4OC)ccnc3[nH]2)CC1
InChIKey: ZPUBPIPZFAUDSS-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human A-431 cells assessed as reduction in RNA polymerase2 phosphorylation at C-terminal ser2 residue incubated for 4 hrs by In-cell Western analysis
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 380.42, ALogP 3.81, HBA 3, HBD 2, PSA 70.25, QED 0.73
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCC(C(=O)O)CC3)cc12
InChIKey: DPGRHRYLFMBPHK-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human A-431 cells assessed as reduction in RNA polymerase2 phosphorylation at C-terminal ser2 residue incubated for 4 hrs by In-cell Western analysis
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 366.39, ALogP 4.65, HBA 3, HBD 2, PSA 75.21, QED 0.7
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN(CC(=O)O)CC3)cc12
InChIKey: POISLEHCMDEHNV-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 381.41, ALogP 3.55, HBA 4, HBD 2, PSA 78.45, QED 0.71
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCC(N[C@@H](C(=O)O)C(C)C)CC3)cc12
InChIKey: VKEWATIKYFEHIF-IRCUZVAFSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin) using Ulight-labeled substrate measured after 1.5 hrs by TR-FRET LANCE method
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 437.52, ALogP 5.01, HBA 4, HBD 3, PSA 87.24, QED 0.48
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN([C@H]4CC[C@@H](CC(=O)O)CC4)CC3)cc12
InChIKey: DZZGVCFHAAYUAE-MSEWRSJXSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human A-431 cells assessed as reduction in RNA polymerase2 phosphorylation at C-terminal ser2 residue incubated for 4 hrs by In-cell Western analysis
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 463.55, ALogP 5.5, HBA 4, HBD 2, PSA 78.45, QED 0.5
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN([C@H]4CC[C@H](CC(=O)O)CC4)CC3)cc12
InChIKey: DZZGVCFHAAYUAE-IRJFHVNHSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human A-431 cells assessed as reduction in RNA polymerase2 phosphorylation at C-terminal ser2 residue incubated for 4 hrs by In-cell Western analysis
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 463.55, ALogP 5.5, HBA 4, HBD 2, PSA 78.45, QED 0.5
Compound (SMILES): C[C@H](NC(=O)C(C)(F)F)[C@H](Oc1ccc2c(cnn2-c2cccc(C(=O)N[C@@H]3CCS(=O)(=O)C3)c2)c1)c1ccc2c(c1)OCCO2
InChIKey: VPLFURZOENDKIP-BWGXUDETSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Displacement of [3H]-aldosterone from N terminal maltose binding protein tagged human mineralocorticoid receptor LBD (726 to 984 residues) expressed in baculovirus infected high five cells after 8 hrs by scintillation proximity assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 654.69, ALogP 3.99, HBA 9, HBD 2, PSA 137.85, QED 0.28
Compound (SMILES): C[C@H](NC(=O)C(C)(F)F)[C@H](Oc1ccc2c(cnn2-c2cccc(C(=O)N[C@@H]3CCOC3)c2)c1)c1ccc2c(c1)OCCO2
InChIKey: ZZWJKLGCDHYVMB-BWGXUDETSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Displacement of [3H]-aldosterone from N terminal maltose binding protein tagged human mineralocorticoid receptor LBD (726 to 984 residues) expressed in baculovirus infected high five cells after 8 hrs by scintillation proximity assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 606.63, ALogP 4.6, HBA 8, HBD 2, PSA 112.94, QED 0.29