lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(Cl)cc1-c1c(NC(=O)c2cnn3cccnc23)cnn1CCO
InChIKey: JWMNWMLDJKHWSK-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 = 5.6 nM (pChEMBL 8.25)
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: 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 = 38.5 nM (pChEMBL 7.420000076293945)
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 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 = 2.6 nM (pChEMBL 8.59000015258789)
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: 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 = 1.5 nM (pChEMBL 8.819999694824219)
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: 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 = 2.1 nM (pChEMBL 8.680000305175781)
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: 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 = 775 nM (pChEMBL 6.110000133514404)
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 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 = 2.1 nM (pChEMBL 8.680000305175781)
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: 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 = 9.1 nM (pChEMBL 8.039999961853027)
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 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 = 2.5 nM (pChEMBL 8.600000381469727)
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: 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 = 4.2 nM (pChEMBL 8.380000114440918)
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: 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 = 47 nM (pChEMBL 7.329999923706055)
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: 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 = 85.9 nM (pChEMBL 7.070000171661377)
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: 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 = 230 nM (pChEMBL 6.639999866485596)
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: 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 = 76 nM (pChEMBL 7.119999885559082)
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 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 = 1.5 nM (pChEMBL 8.819999694824219)
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: 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 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 454.88, ALogP 1.99, HBA 9, HBD 1, PSA 119.54, QED 0.47
Compound (SMILES): O=C(CC1CN2CCC1CC2)Nc1cc2cccc(Br)c2s1
InChIKey: KEUPMWVOFFHALI-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Binding Assay: Rat brain tissue (hippocampus or whole brain) is homogenized in homogenization buffer (10% w/v). [0.32 M sucrose, 1 mM EDTA; 0.1 mM phenylmethylsulfonyl fluoride (PMSF), 0.01% (w/v) NaN3, pH 7.4, 4 C.] at 600 rpm in a glass homogenizer. The homogenate is centrifuged (1000xg, 4 C., 10 min) and the supernatant is removed. The pellet is resuspended (20% w/v) and the suspension is centrifuged (1000xg, 4 C., 10 mM). The two supernatants are combined and centrifuged (15 000xg, 4 C., 30 min). The pellet obtained in this way is referred to as the P2 fraction.The P2 pellet is washed twice with binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and centrifuged (15 000xg, 4 C., 30 min).The P2 membranes are resuspended in binding buffer and incubated in a volume of 250 ul (amount of membrane protein 0.1-0.5 mg) in the presence of 1-5 nM [3H]methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance.
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 379.32, ALogP 4.33, HBA 3, HBD 1, PSA 32.34, QED 0.86
Compound (SMILES): O=C(CC1CN2CCC1CC2)Nc1cc2ccc(Br)cc2s1
InChIKey: RBXQEDNOVSSTPK-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Binding Assay: Rat brain tissue (hippocampus or whole brain) is homogenized in homogenization buffer (10% w/v). [0.32 M sucrose, 1 mM EDTA; 0.1 mM phenylmethylsulfonyl fluoride (PMSF), 0.01% (w/v) NaN3, pH 7.4, 4 C.] at 600 rpm in a glass homogenizer. The homogenate is centrifuged (1000xg, 4 C., 10 min) and the supernatant is removed. The pellet is resuspended (20% w/v) and the suspension is centrifuged (1000xg, 4 C., 10 mM). The two supernatants are combined and centrifuged (15 000xg, 4 C., 30 min). The pellet obtained in this way is referred to as the P2 fraction.The P2 pellet is washed twice with binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and centrifuged (15 000xg, 4 C., 30 min).The P2 membranes are resuspended in binding buffer and incubated in a volume of 250 ul (amount of membrane protein 0.1-0.5 mg) in the presence of 1-5 nM [3H]methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance.
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 379.32, ALogP 4.33, HBA 3, HBD 1, PSA 32.34, QED 0.86
Compound (SMILES): O=C(CC1CN2CCC1CC2)Nc1ccc2cccnc2c1
InChIKey: WCKPVMZWEVYPSV-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Binding Assay: Rat brain tissue (hippocampus or whole brain) is homogenized in homogenization buffer (10% w/v). [0.32 M sucrose, 1 mM EDTA; 0.1 mM phenylmethylsulfonyl fluoride (PMSF), 0.01% (w/v) NaN3, pH 7.4, 4 C.] at 600 rpm in a glass homogenizer. The homogenate is centrifuged (1000xg, 4 C., 10 min) and the supernatant is removed. The pellet is resuspended (20% w/v) and the suspension is centrifuged (1000xg, 4 C., 10 mM). The two supernatants are combined and centrifuged (15 000xg, 4 C., 30 min). The pellet obtained in this way is referred to as the P2 fraction.The P2 pellet is washed twice with binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and centrifuged (15 000xg, 4 C., 30 min).The P2 membranes are resuspended in binding buffer and incubated in a volume of 250 ul (amount of membrane protein 0.1-0.5 mg) in the presence of 1-5 nM [3H]methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance.
Measurement: Ki = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 295.39, ALogP 2.91, HBA 3, HBD 1, PSA 45.23, QED 0.95
Compound (SMILES): O=C(CC1CN2CCC1CC2)Nc1ccc2ccccc2c1
InChIKey: ABKOUBVDJMBBLY-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Binding Assay: Rat brain tissue (hippocampus or whole brain) is homogenized in homogenization buffer (10% w/v). [0.32 M sucrose, 1 mM EDTA; 0.1 mM phenylmethylsulfonyl fluoride (PMSF), 0.01% (w/v) NaN3, pH 7.4, 4 C.] at 600 rpm in a glass homogenizer. The homogenate is centrifuged (1000xg, 4 C., 10 min) and the supernatant is removed. The pellet is resuspended (20% w/v) and the suspension is centrifuged (1000xg, 4 C., 10 mM). The two supernatants are combined and centrifuged (15 000xg, 4 C., 30 min). The pellet obtained in this way is referred to as the P2 fraction.The P2 pellet is washed twice with binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and centrifuged (15 000xg, 4 C., 30 min).The P2 membranes are resuspended in binding buffer and incubated in a volume of 250 ul (amount of membrane protein 0.1-0.5 mg) in the presence of 1-5 nM [3H]methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance.
Measurement: Ki = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 294.4, ALogP 3.51, HBA 2, HBD 1, PSA 32.34, QED 0.94
Compound (SMILES): O=C(CC1CN2CCC1CC2)Nc1ccc2cccc([N+](=O)[O-])c2c1
InChIKey: VWRXYQBZFOQNPP-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Binding Assay: Rat brain tissue (hippocampus or whole brain) is homogenized in homogenization buffer (10% w/v). [0.32 M sucrose, 1 mM EDTA; 0.1 mM phenylmethylsulfonyl fluoride (PMSF), 0.01% (w/v) NaN3, pH 7.4, 4 C.] at 600 rpm in a glass homogenizer. The homogenate is centrifuged (1000xg, 4 C., 10 min) and the supernatant is removed. The pellet is resuspended (20% w/v) and the suspension is centrifuged (1000xg, 4 C., 10 mM). The two supernatants are combined and centrifuged (15 000xg, 4 C., 30 min). The pellet obtained in this way is referred to as the P2 fraction.The P2 pellet is washed twice with binding buffer (50 mM Tris-HCl, 1 mM MgCl2, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, pH 7.4), and centrifuged (15 000xg, 4 C., 30 min).The P2 membranes are resuspended in binding buffer and incubated in a volume of 250 ul (amount of membrane protein 0.1-0.5 mg) in the presence of 1-5 nM [3H]methyllycaconitine, 0.1% (w/v) BSA (bovine serum albumin) and various concentrations of the test substance.
Measurement: Ki = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 339.4, ALogP 3.42, HBA 4, HBD 1, PSA 75.48, QED 0.68
Compound (SMILES): COCCOc1cc(Cl)c(C(=O)NCc2ccc(-c3cc[nH]c(=O)c3)cc2)c(Cl)c1
InChIKey: LHRZBKAEDZUYNC-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 447.32, ALogP 4.3, HBA 4, HBD 2, PSA 80.42, QED 0.5
Compound (SMILES): O=C(NCc1ccc(-c2cc[nH]c(=O)c2)cc1)c1c(Cl)cccc1Cl
InChIKey: MROYYAOBHCNTQW-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 373.24, ALogP 4.28, HBA 2, HBD 2, PSA 61.96, QED 0.72
Compound (SMILES): O=C(NCc1ccc(-c2cc[nH]c(=O)c2)cc1)c1cccc(F)c1Cl
InChIKey: MQNHFYLSWQUUNV-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 356.78, ALogP 3.76, HBA 2, HBD 2, PSA 61.96, QED 0.75
Compound (SMILES): Cc1cccc(Cl)c1C(=O)NCc1ccc(-c2cc[nH]c(=O)c2)cc1
InChIKey: RGVVJYOVGIKMLY-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 352.82, ALogP 3.93, HBA 2, HBD 2, PSA 61.96, QED 0.75
Compound (SMILES): Cc1cccc(C)c1C(=O)NCc1ccc(-c2cc[nH]c(=O)c2)cc1
InChIKey: ZTQCTWHLFXVYGO-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 166 nM (pChEMBL 6.78000020980835)
Descriptors: MW 332.4, ALogP 3.59, HBA 2, HBD 2, PSA 61.96, QED 0.77
Compound (SMILES): Cc1cc(-c2ccc(CNC(=O)c3c(Cl)cccc3Cl)cc2)cc(=O)[nH]1
InChIKey: LWYWZWJVXJWUFS-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 1113 nM (pChEMBL 5.949999809265137)
Descriptors: MW 387.27, ALogP 4.59, HBA 2, HBD 2, PSA 61.96, QED 0.69
Compound (SMILES): O=C(NCc1ccc(-c2cc[nH]c(=O)c2)cc1)c1c(F)ccc(F)c1Cl
InChIKey: SFVKNPJMMRPOCO-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: ALDH2 Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 374.77, ALogP 3.9, HBA 2, HBD 2, PSA 61.96, QED 0.68
Compound (SMILES): Cc1cc(CNC(=O)c2c(Cl)cccc2Cl)ccc1-c1cc[nH]c(=O)c1
InChIKey: CDCUWQFSGRLNTF-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 387.27, ALogP 4.59, HBA 2, HBD 2, PSA 61.96, QED 0.69
Compound (SMILES): Cn1ccc(-c2ccc(CNC(=O)c3c(Cl)cccc3Cl)cc2)cc1=O
InChIKey: SNIYXAMBBPVCFT-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 2093 nM (pChEMBL 5.679999828338623)
Descriptors: MW 387.27, ALogP 4.29, HBA 3, HBD 1, PSA 51.1, QED 0.73
Compound (SMILES): O=C(NCc1ccc(-c2cc[nH]c(=O)c2)cc1)c1c(F)cccc1F
InChIKey: JOUVKEHJJRSRSI-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 890 nM (pChEMBL 6.050000190734863)
Descriptors: MW 340.33, ALogP 3.25, HBA 2, HBD 2, PSA 61.96, QED 0.77
Compound (SMILES): O=C(NCc1ccc(-c2cc[nH]c(=O)c2)cc1)c1c(F)cccc1Cl
InChIKey: BTYCFCPAVPVWMT-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 379 nM (pChEMBL 6.420000076293945)
Descriptors: MW 356.78, ALogP 3.76, HBA 2, HBD 2, PSA 61.96, QED 0.75
Compound (SMILES): O=C(NCc1ccc(-c2cc[nH]c(=O)c2)cc1F)c1c(Cl)cccc1Cl
InChIKey: JJLNHGOWLAKMNE-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 304 nM (pChEMBL 6.519999980926514)
Descriptors: MW 391.23, ALogP 4.42, HBA 2, HBD 2, PSA 61.96, QED 0.69
Compound (SMILES): O=C(NCc1ccc(-c2cc(=O)[nH]cc2F)cc1)c1c(Cl)cccc1Cl
InChIKey: CMKJXIYFWVLQAC-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 391.23, ALogP 4.42, HBA 2, HBD 2, PSA 61.96, QED 0.69
Compound (SMILES): O=C(NCc1ccc(-c2ccn(COP(=O)(O)O)c(=O)c2)cc1)c1c(Cl)cccc1Cl
InChIKey: SPADNYVJQZNTKZ-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition Assay: Standard ALDH2 reaction mixtures contained 150 uM formaldehyde, 2.5 mM NAD+, 10 mM MgCl2 and 10 nM recombinant human ALDH2 in 50 mM Hepes buffer, pH 7.4, 0.01% Tween 20 in a final volume of 50 ul using 384-well plates. After 60 min of pre-incubation of compound with ALDH2 and formaldehyde, the reaction was started by adding NAD+ and the reaction mixture was allowed to proceed for 90 minutes. Activity of the enzyme was determined by monitoring NADH formation using Perkin-Elmer Envision Reader with excitation and emission wavelengths set at 340 and 460 nm, respectively.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 483.24, ALogP 3.82, HBA 5, HBD 3, PSA 117.86, QED 0.44
Compound (SMILES): CSc1cccc(NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccc(Br)s2)c1
InChIKey: GGCRLIFVACLEJF-ZDUSSCGKSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
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 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 461.43, ALogP 4.02, HBA 5, HBD 1, PSA 66.48, QED 0.68
Compound (SMILES): O=C(Nc1cccc(OC(F)(F)F)c1)[C@@H]1CCCN1S(=O)(=O)c1ccc(Br)s1
InChIKey: UQKUYLQAURTPEX-LBPRGKRZSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
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 = 149 nM (pChEMBL 6.829999923706055)
Descriptors: MW 499.33, ALogP 4.2, HBA 5, HBD 1, PSA 75.71, QED 0.67
Compound (SMILES): COc1cccc(S(=O)(=O)N2CCC[C@H]2C(=O)Nc2cccc(SC)c2)c1
InChIKey: MENYSNIOINZHOK-SFHVURJKSA-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 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 406.53, ALogP 3.21, HBA 5, HBD 1, PSA 75.71, QED 0.75
Compound (SMILES): CCCc1ccc(S(=O)(=O)N2CCC[C@H]2C(=O)Nc2cccc(SC)c2)cc1
InChIKey: WLTRYFFFSCLNPW-FQEVSTJZSA-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 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 418.58, ALogP 4.15, HBA 4, HBD 1, PSA 66.48, QED 0.69
Compound (SMILES): CSc1cccc(NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccc3c(c2)OCCN3C)c1
InChIKey: GIKLPDMPMGWEOB-IBGZPJMESA-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 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 447.58, ALogP 3.03, HBA 6, HBD 1, PSA 78.95, QED 0.71
Compound (SMILES): COc1ccc(S(=O)(=O)N2CCC[C@H]2C(=O)Nc2cccc(SC)c2)cc1
InChIKey: DIUDVHGBTFDFCN-SFHVURJKSA-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 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 406.53, ALogP 3.21, HBA 5, HBD 1, PSA 75.71, QED 0.75