lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc(-c2n[nH]c3cc(NC(=O)N[C@@H](CN(C)C)c4ccccc4)ncc23)ccn1
InChIKey: XSQMERQMENMOIR-FQEVSTJZSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 10.84 nM (pChEMBL 7.960000038146973)
Descriptors: MW 415.5, ALogP 3.75, HBA 5, HBD 3, PSA 98.83, QED 0.45
Compound (SMILES): Cc1cc(-c2n[nH]c3cc(NC(=O)N[C@H](CN(C)C)c4ccccc4)ncc23)ccn1
InChIKey: XSQMERQMENMOIR-HXUWFJFHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 0.2904 nM (pChEMBL 9.539999961853027)
Descriptors: MW 415.5, ALogP 3.75, HBA 5, HBD 3, PSA 98.83, QED 0.45
Compound (SMILES): Cc1cc(-c2n[nH]c3cc(NC(=O)N[C@H](CN)c4ccccc4)ncc23)ccn1
InChIKey: XNLZRLFOJHEWFI-GOSISDBHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 0.1524 nM (pChEMBL 9.819999694824219)
Descriptors: MW 387.45, ALogP 3.15, HBA 5, HBD 4, PSA 121.61, QED 0.42
Compound (SMILES): Cc1cc(-c2n[nH]c3cc(NC(=O)NCC4CCO4)ncc23)ccn1
InChIKey: VKIOGFFJNUMYKQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 376.2 nM (pChEMBL 6.420000076293945)
Descriptors: MW 338.37, ALogP 2.24, HBA 5, HBD 3, PSA 104.82, QED 0.68
Compound (SMILES): COc1cccc(F)c1CNC(=O)Nc1cc2[nH]nc(-c3ccnc(C)c3)c2cn1
InChIKey: FPBQVWRUEOQHTQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 0.3067 nM (pChEMBL 9.510000228881836)
Descriptors: MW 406.42, ALogP 3.8, HBA 5, HBD 3, PSA 104.82, QED 0.47
Compound (SMILES): COC[C@H](NC(=O)Nc1cc2[nH]nc(-c3ccc(F)cc3)c2cn1)c1ccccn1
InChIKey: WBHXUEAXCYZFRF-SFHVURJKSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 23.52 nM (pChEMBL 7.630000114440918)
Descriptors: MW 406.42, ALogP 3.67, HBA 5, HBD 3, PSA 104.82, QED 0.45
Compound (SMILES): Cc1cc(-c2n[nH]c3cc(NC(=O)NCc4ncc(Cl)cc4F)ncc23)ccn1
InChIKey: WKTDTAWFUWPQJN-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 10.13 nM (pChEMBL 7.989999771118164)
Descriptors: MW 411.83, ALogP 3.84, HBA 5, HBD 3, PSA 108.48, QED 0.47
Compound (SMILES): Cc1cc(-c2n[nH]c3cc(NC(=O)NCc4csc5ccc(Cl)cc45)ncc23)ccn1
InChIKey: XZVCLYAPGOSVBG-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 5.853 nM (pChEMBL 8.229999542236328)
Descriptors: MW 448.94, ALogP 5.52, HBA 5, HBD 3, PSA 95.59, QED 0.34
Compound (SMILES): Cc1cc(-c2n[nH]c3cc(NC(=O)NC4CNCc5ccccc54)ccc23)ccn1
InChIKey: CAHWPRRMZJUULV-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 1.201 nM (pChEMBL 8.920000076293945)
Descriptors: MW 398.47, ALogP 3.9, HBA 4, HBD 4, PSA 94.73, QED 0.42
Compound (SMILES): Cc1cc(-c2n[nH]c3cc(NC(=O)N[C@@H]4c5ccccc5C[C@H]4N(C)C)ncc23)ccn1
InChIKey: INNCEEWCCXYWLR-NFBKMPQASA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: IMAP-FP Assay: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. To each well of a black Corning 384-well plate (Corning Catalog #3575), 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was dispensed, followed by the addition of 15 uL of kinase buffer (tween containing kinase buffer, Molecular Devices) containing 0.0364 ng/mL (0.833 nM) of phosphorylated active hERK2 enzyme. Following a 15 minute compound & enzyme incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP.
Measurement: IC50 = 11.29 nM (pChEMBL 7.949999809265137)
Descriptors: MW 427.51, ALogP 3.68, HBA 5, HBD 3, PSA 98.83, QED 0.46
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](NS(=O)(=O)N2C[C@H]3C[C@@]3(C#N)C2)C1
InChIKey: KITABLLENVFMQT-KOFHJDLBSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 = 551 nM (pChEMBL 6.260000228881836)
Descriptors: MW 387.47, ALogP 0.6, HBA 6, HBD 2, PSA 118.01, QED 0.78
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@H](NS(=O)(=O)N2CCC(C#N)C2)C1
InChIKey: UYSGAWMQMRAGJH-VLXSWZPNSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 375.46, ALogP 0.6, HBA 6, HBD 2, PSA 118.01, QED 0.79
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](CS(=O)(=O)N2CCC(F)(F)CC2)C1
InChIKey: KZSUFPIJESVIGH-BETUJISGSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 399.47, ALogP 2.23, HBA 5, HBD 1, PSA 82.19, QED 0.83
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](CS(=O)(=O)N2CCC(O)(C(F)(F)F)CC2)C1
InChIKey: AHTMSATVFMHGNS-BETUJISGSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 447.48, ALogP 1.89, HBA 6, HBD 2, PSA 102.42, QED 0.73
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](CS(=O)(=O)N2CC[C@@H](C#N)C2)C1
InChIKey: WVPXLLNKSSQYKI-MELADBBJSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 = 5270 nM (pChEMBL 5.28000020980835)
Descriptors: MW 374.47, ALogP 1.35, HBA 6, HBD 1, PSA 105.98, QED 0.85
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](CS(=O)(=O)N2CC[C@H](C#N)C2)C1
InChIKey: WVPXLLNKSSQYKI-MCIONIFRSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 > 9930 nM (pChEMBL 5.002999782562256)
Descriptors: MW 374.47, ALogP 1.35, HBA 6, HBD 1, PSA 105.98, QED 0.85
Compound (SMILES): CCCCS(=O)(=O)C[C@H]1C[C@@H](N(C)c2ncnc3[nH]ccc23)C1
InChIKey: MWMGOQSAHFDXOV-BETUJISGSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 = 553 nM (pChEMBL 6.260000228881836)
Descriptors: MW 336.46, ALogP 2.39, HBA 5, HBD 1, PSA 78.95, QED 0.84
Compound (SMILES): CCCS(=O)(=O)C[C@H]1C[C@H](N(C)c2ncnc3[nH]ccc23)C1
InChIKey: JXXOAWDMPAWACX-HAQNSBGRSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 322.43, ALogP 2, HBA 5, HBD 1, PSA 78.95, QED 0.88
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](CS(=O)(=O)CCC2CC2)C1
InChIKey: AYQMQHMCFYCBTJ-OKILXGFUSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 348.47, ALogP 2.39, HBA 5, HBD 1, PSA 78.95, QED 0.83
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](CS(=O)(=O)CC2CC(F)(F)C2)C1
InChIKey: RQYJLWOKIRQLAA-BJHJDKERSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 = 6570 nM (pChEMBL 5.179999828338623)
Descriptors: MW 384.45, ALogP 2.63, HBA 5, HBD 1, PSA 78.95, QED 0.83
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](CS(=O)(=O)[C@H]2CC[C@H](C#N)C2)C1
InChIKey: HRRLZKHIEGDCQZ-XQLPTFJDSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 373.48, ALogP 2.28, HBA 6, HBD 1, PSA 102.74, QED 0.86
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](CS(=O)(=O)[C@@H]2CC[C@@H](C#N)C2)C1
InChIKey: HRRLZKHIEGDCQZ-APIJFGDWSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 373.48, ALogP 2.28, HBA 6, HBD 1, PSA 102.74, QED 0.86
Compound (SMILES): CC(C)N1CCC(S(=O)(=O)C[C@H]2C[C@@H](N(C)c3ncnc4[nH]ccc34)C2)C1
InChIKey: PMBVJRGBYOKWGM-XYPWUTKMSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 = 3760 nM (pChEMBL 5.420000076293945)
Descriptors: MW 391.54, ALogP 2.07, HBA 6, HBD 1, PSA 82.19, QED 0.81
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](CS(=O)(=O)c2ccc(F)c(Cl)c2)C1
InChIKey: UDIPEBURYXADGV-TXEJJXNPSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 408.89, ALogP 3.44, HBA 5, HBD 1, PSA 78.95, QED 0.65
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](CS(=O)(=O)c2cc(C#N)ccn2)C1
InChIKey: ISQGUVXYSCPBBI-OKILXGFUSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 = 418 nM (pChEMBL 6.380000114440918)
Descriptors: MW 382.45, ALogP 1.91, HBA 7, HBD 1, PSA 115.63, QED 0.72
Compound (SMILES): Cc1ncc(S(=O)(=O)N[C@H]2C[C@@H](N(C)c3ncnc4[nH]ccc34)C2)s1
InChIKey: XHRZECXFXFEXHN-PHIMTYICSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: Test article and assay controls were added to a 384-well plate. Reaction mixtures contained 20 mM HEPES, pH 7.4, 10 mM magnesium chloride, 0.01% bovine serum albumin (BSA), 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAMKKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK3 or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20%-30% phosphorylation. The assays were stopped with a final concentration of 10 mM EDTA, 0.1% Coating Reagent and 100 mM HEPES, pH=7.4.
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 378.48, ALogP 1.67, HBA 7, HBD 2, PSA 103.87, QED 0.7
Compound (SMILES): O=C1NCC=CCN1[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F
InChIKey: SNRKAOGJCXPPSV-BWZBUEFSSA-N
Target: Cytidine deaminase (SINGLE PROTEIN), Homo sapiens
UniProt: P32320
Assay: Enzymatic Assay: The cytidine deaminase (CDA) enzymatic assay described by Cacciamani, T. et al., Arch. Biochem. Biophys. 1991, 290, 285-92; Cohen R. et al., J. Biol. Chem., 1971, 246, 7566-8; and Vincenzetti S. et al., Protein Expr. Purif. 1996, 8, 247-53 was used to determine the inhibitory activity (IC50) of compounds described herein. Using this assay, the IC50 of these compounds was determined by following the decrease of substrate (cytidine) caused by the deamination reaction catalyzed by CDA. Disappearance of substrate (cytidine) over time was monitored by the absorbance at 280 nm of the reaction. The assay reaction was carried out in potassium phosphate buffer (pH 7.4, 20 mM, containing 1 mM DTT) in a total volume of 100 ul in a 96-well plate format. The final reaction mixture contained cytidine (50 uM) and purified human recombinant CDA. Purified enzyme was diluted so as to produce an absorbance change of approximately 2 milli-absorbance units/minute.
Measurement: IC50 = 237 nM (pChEMBL 6.619999885559082)
Descriptors: MW 264.23, ALogP -0.72, HBA 4, HBD 3, PSA 82.03, QED 0.57
Compound (SMILES): O=C1NCC=CCN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
InChIKey: HBBIVXDEBCKFIZ-FNCVBFRFSA-N
Target: Cytidine deaminase (SINGLE PROTEIN), Homo sapiens
UniProt: P32320
Assay: Enzymatic Assay: The cytidine deaminase (CDA) enzymatic assay described by Cacciamani, T. et al., Arch. Biochem. Biophys. 1991, 290, 285-92; Cohen R. et al., J. Biol. Chem., 1971, 246, 7566-8; and Vincenzetti S. et al., Protein Expr. Purif. 1996, 8, 247-53 was used to determine the inhibitory activity (IC50) of compounds described herein. Using this assay, the IC50 of these compounds was determined by following the decrease of substrate (cytidine) caused by the deamination reaction catalyzed by CDA. Disappearance of substrate (cytidine) over time was monitored by the absorbance at 280 nm of the reaction. The assay reaction was carried out in potassium phosphate buffer (pH 7.4, 20 mM, containing 1 mM DTT) in a total volume of 100 ul in a 96-well plate format. The final reaction mixture contained cytidine (50 uM) and purified human recombinant CDA. Purified enzyme was diluted so as to produce an absorbance change of approximately 2 milli-absorbance units/minute.
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 244.25, ALogP -1.99, HBA 5, HBD 4, PSA 102.26, QED 0.42
Compound (SMILES): O=C1NCC=CCN1[C@H]1O[C@H](CO)[C@@H](O)C1(F)F
InChIKey: SNRKAOGJCXPPSV-PRJMDXOYSA-N
Target: Cytidine deaminase (SINGLE PROTEIN), Homo sapiens
UniProt: P32320
Assay: Enzymatic Assay: The cytidine deaminase (CDA) enzymatic assay described by Cacciamani, T. et al., Arch. Biochem. Biophys. 1991, 290, 285-92; Cohen R. et al., J. Biol. Chem., 1971, 246, 7566-8; and Vincenzetti S. et al., Protein Expr. Purif. 1996, 8, 247-53 was used to determine the inhibitory activity (IC50) of compounds described herein. Using this assay, the IC50 of these compounds was determined by following the decrease of substrate (cytidine) caused by the deamination reaction catalyzed by CDA. Disappearance of substrate (cytidine) over time was monitored by the absorbance at 280 nm of the reaction. The assay reaction was carried out in potassium phosphate buffer (pH 7.4, 20 mM, containing 1 mM DTT) in a total volume of 100 ul in a 96-well plate format. The final reaction mixture contained cytidine (50 uM) and purified human recombinant CDA. Purified enzyme was diluted so as to produce an absorbance change of approximately 2 milli-absorbance units/minute.
Measurement: IC50 = 1616 nM (pChEMBL 5.789999961853027)
Descriptors: MW 264.23, ALogP -0.72, HBA 4, HBD 3, PSA 82.03, QED 0.57
Compound (SMILES): O=C1NCC=CCN1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1F
InChIKey: FHJRJJBDJACZGH-BZNPZCIMSA-N
Target: Cytidine deaminase (SINGLE PROTEIN), Homo sapiens
UniProt: P32320
Assay: Enzymatic Assay: The cytidine deaminase (CDA) enzymatic assay described by Cacciamani, T. et al., Arch. Biochem. Biophys. 1991, 290, 285-92; Cohen R. et al., J. Biol. Chem., 1971, 246, 7566-8; and Vincenzetti S. et al., Protein Expr. Purif. 1996, 8, 247-53 was used to determine the inhibitory activity (IC50) of compounds described herein. Using this assay, the IC50 of these compounds was determined by following the decrease of substrate (cytidine) caused by the deamination reaction catalyzed by CDA. Disappearance of substrate (cytidine) over time was monitored by the absorbance at 280 nm of the reaction. The assay reaction was carried out in potassium phosphate buffer (pH 7.4, 20 mM, containing 1 mM DTT) in a total volume of 100 ul in a 96-well plate format. The final reaction mixture contained cytidine (50 uM) and purified human recombinant CDA. Purified enzyme was diluted so as to produce an absorbance change of approximately 2 milli-absorbance units/minute.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 246.24, ALogP -1.02, HBA 4, HBD 3, PSA 82.03, QED 0.54
Compound (SMILES): CCCC[C@]1(CC)CS(=O)(=O)c2cc(C)c(OC)cc2[C@@H](c2ccccc2)N1
InChIKey: IPWYFVPPJJWMNS-DHIUTWEWSA-N
Target: Ileal sodium/bile acid cotransporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q12908
Assay: Inhibition Assay: On the day of the uptake experiment, 10 mM HEPES was added to Hank's Balanced Salt Solution, and the pH was adjusted to 7.4 with TRIS (HBSSH). The assay buffer was prepared by adding 100 uM [3H]-taurocholate and 10 uM cold taurocholate to room temperature HBSSH. A separate washing buffer was prepared by adding 10 uM cold taurocholate to HBSSH (30 ml per assay plate) and placed on ice. Using 100% DMSO, 8 point, 3-fold dilution curves for each test compound was prepared starting at 200 uM. Similarly, an 8 point dose response curve was prepared of the control compound [(3R,5R)-3-butyl-3-ethyl-7,8-bis(methyloxy)-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (Brieaddy, L. E. WO9605188, 1996)] starting at 1.8 mM. Drug plates were created by adding 3 uL of each concentration to a v-bottom 96-well plate then diluted 60-fold with 177 uL of assay buffer. Plates were removed from the incubator and allowed to cool to ambient temperature.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 401.57, ALogP 4.81, HBA 4, HBD 1, PSA 55.4, QED 0.75
Compound (SMILES): CCCC[C@]1(CC)CS(=O)(=O)c2cc(C(N)=O)c(OC)cc2[C@@H](c2ccccc2)N1
InChIKey: NJGBVIUDIFQUNF-FYYLOGMGSA-N
Target: Ileal sodium/bile acid cotransporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q12908
Assay: Inhibition Assay: On the day of the uptake experiment, 10 mM HEPES was added to Hank's Balanced Salt Solution, and the pH was adjusted to 7.4 with TRIS (HBSSH). The assay buffer was prepared by adding 100 uM [3H]-taurocholate and 10 uM cold taurocholate to room temperature HBSSH. A separate washing buffer was prepared by adding 10 uM cold taurocholate to HBSSH (30 ml per assay plate) and placed on ice. Using 100% DMSO, 8 point, 3-fold dilution curves for each test compound was prepared starting at 200 uM. Similarly, an 8 point dose response curve was prepared of the control compound [(3R,5R)-3-butyl-3-ethyl-7,8-bis(methyloxy)-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (Brieaddy, L. E. WO9605188, 1996)] starting at 1.8 mM. Drug plates were created by adding 3 uL of each concentration to a v-bottom 96-well plate then diluted 60-fold with 177 uL of assay buffer. Plates were removed from the incubator and allowed to cool to ambient temperature.
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 430.57, ALogP 3.6, HBA 5, HBD 2, PSA 98.49, QED 0.7
Compound (SMILES): C=Cc1cc2c(cc1OC)[C@@H](c1ccccc1)N[C@](CC)(CCCC)CS2(=O)=O
InChIKey: UULJKKGMHQPNOS-DNQXCXABSA-N
Target: Ileal sodium/bile acid cotransporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q12908
Assay: Inhibition Assay: On the day of the uptake experiment, 10 mM HEPES was added to Hank's Balanced Salt Solution, and the pH was adjusted to 7.4 with TRIS (HBSSH). The assay buffer was prepared by adding 100 uM [3H]-taurocholate and 10 uM cold taurocholate to room temperature HBSSH. A separate washing buffer was prepared by adding 10 uM cold taurocholate to HBSSH (30 ml per assay plate) and placed on ice. Using 100% DMSO, 8 point, 3-fold dilution curves for each test compound was prepared starting at 200 uM. Similarly, an 8 point dose response curve was prepared of the control compound [(3R,5R)-3-butyl-3-ethyl-7,8-bis(methyloxy)-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (Brieaddy, L. E. WO9605188, 1996)] starting at 1.8 mM. Drug plates were created by adding 3 uL of each concentration to a v-bottom 96-well plate then diluted 60-fold with 177 uL of assay buffer. Plates were removed from the incubator and allowed to cool to ambient temperature.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 413.58, ALogP 5.14, HBA 4, HBD 1, PSA 55.4, QED 0.68
Compound (SMILES): CCCC[C@]1(CC)CS(=O)(=O)c2cc(CC)c(OC)cc2[C@@H](c2ccccc2)N1
InChIKey: DYNJCBHXKBPNII-DNQXCXABSA-N
Target: Ileal sodium/bile acid cotransporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q12908
Assay: Inhibition Assay: On the day of the uptake experiment, 10 mM HEPES was added to Hank's Balanced Salt Solution, and the pH was adjusted to 7.4 with TRIS (HBSSH). The assay buffer was prepared by adding 100 uM [3H]-taurocholate and 10 uM cold taurocholate to room temperature HBSSH. A separate washing buffer was prepared by adding 10 uM cold taurocholate to HBSSH (30 ml per assay plate) and placed on ice. Using 100% DMSO, 8 point, 3-fold dilution curves for each test compound was prepared starting at 200 uM. Similarly, an 8 point dose response curve was prepared of the control compound [(3R,5R)-3-butyl-3-ethyl-7,8-bis(methyloxy)-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (Brieaddy, L. E. WO9605188, 1996)] starting at 1.8 mM. Drug plates were created by adding 3 uL of each concentration to a v-bottom 96-well plate then diluted 60-fold with 177 uL of assay buffer. Plates were removed from the incubator and allowed to cool to ambient temperature.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 415.6, ALogP 5.06, HBA 4, HBD 1, PSA 55.4, QED 0.69
Compound (SMILES): CCCC[C@]1(CC)CS(=O)(=O)c2cc(CCC(=O)NS(C)(=O)=O)c(OC)cc2[C@@H](c2ccccc2)N1
InChIKey: OUCRMKLLTCNFBX-CLJLJLNGSA-N
Target: Ileal sodium/bile acid cotransporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q12908
Assay: Inhibition Assay: On the day of the uptake experiment, 10 mM HEPES was added to Hank's Balanced Salt Solution, and the pH was adjusted to 7.4 with TRIS (HBSSH). The assay buffer was prepared by adding 100 uM [3H]-taurocholate and 10 uM cold taurocholate to room temperature HBSSH. A separate washing buffer was prepared by adding 10 uM cold taurocholate to HBSSH (30 ml per assay plate) and placed on ice. Using 100% DMSO, 8 point, 3-fold dilution curves for each test compound was prepared starting at 200 uM. Similarly, an 8 point dose response curve was prepared of the control compound [(3R,5R)-3-butyl-3-ethyl-7,8-bis(methyloxy)-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (Brieaddy, L. E. WO9605188, 1996)] starting at 1.8 mM. Drug plates were created by adding 3 uL of each concentration to a v-bottom 96-well plate then diluted 60-fold with 177 uL of assay buffer. Plates were removed from the incubator and allowed to cool to ambient temperature.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 536.72, ALogP 3.51, HBA 7, HBD 2, PSA 118.64, QED 0.48
Compound (SMILES): CCCC[C@]1(CC)CS(=O)(=O)c2cc(CCC(=O)NO)c(OC)cc2[C@@H](c2ccccc2)N1
InChIKey: XLIMLSDWZMJLQW-JWQCQUIFSA-N
Target: Ileal sodium/bile acid cotransporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q12908
Assay: Inhibition Assay: On the day of the uptake experiment, 10 mM HEPES was added to Hank's Balanced Salt Solution, and the pH was adjusted to 7.4 with TRIS (HBSSH). The assay buffer was prepared by adding 100 uM [3H]-taurocholate and 10 uM cold taurocholate to room temperature HBSSH. A separate washing buffer was prepared by adding 10 uM cold taurocholate to HBSSH (30 ml per assay plate) and placed on ice. Using 100% DMSO, 8 point, 3-fold dilution curves for each test compound was prepared starting at 200 uM. Similarly, an 8 point dose response curve was prepared of the control compound [(3R,5R)-3-butyl-3-ethyl-7,8-bis(methyloxy)-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (Brieaddy, L. E. WO9605188, 1996)] starting at 1.8 mM. Drug plates were created by adding 3 uL of each concentration to a v-bottom 96-well plate then diluted 60-fold with 177 uL of assay buffer. Plates were removed from the incubator and allowed to cool to ambient temperature.
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 474.62, ALogP 3.94, HBA 6, HBD 3, PSA 104.73, QED 0.38
Compound (SMILES): CCCC[C@]1(CC)CS(=O)(=O)c2cc(CCC(=O)NC)c(OC)cc2[C@@H](c2ccccc2)N1
InChIKey: UVLBRRQVDQJSLU-CLJLJLNGSA-N
Target: Ileal sodium/bile acid cotransporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q12908
Assay: Inhibition Assay: On the day of the uptake experiment, 10 mM HEPES was added to Hank's Balanced Salt Solution, and the pH was adjusted to 7.4 with TRIS (HBSSH). The assay buffer was prepared by adding 100 uM [3H]-taurocholate and 10 uM cold taurocholate to room temperature HBSSH. A separate washing buffer was prepared by adding 10 uM cold taurocholate to HBSSH (30 ml per assay plate) and placed on ice. Using 100% DMSO, 8 point, 3-fold dilution curves for each test compound was prepared starting at 200 uM. Similarly, an 8 point dose response curve was prepared of the control compound [(3R,5R)-3-butyl-3-ethyl-7,8-bis(methyloxy)-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (Brieaddy, L. E. WO9605188, 1996)] starting at 1.8 mM. Drug plates were created by adding 3 uL of each concentration to a v-bottom 96-well plate then diluted 60-fold with 177 uL of assay buffer. Plates were removed from the incubator and allowed to cool to ambient temperature.
Measurement: IC50 = 276 nM (pChEMBL 6.559999942779541)
Descriptors: MW 472.65, ALogP 4.18, HBA 5, HBD 2, PSA 84.5, QED 0.57
Compound (SMILES): CCCC[C@]1(CC)CS(=O)(=O)c2cc(CCC(=O)NCC)c(OC)cc2[C@@H](c2ccccc2)N1
InChIKey: OMXVOVUJANDZFV-KAYWLYCHSA-N
Target: Ileal sodium/bile acid cotransporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q12908
Assay: Inhibition Assay: On the day of the uptake experiment, 10 mM HEPES was added to Hank's Balanced Salt Solution, and the pH was adjusted to 7.4 with TRIS (HBSSH). The assay buffer was prepared by adding 100 uM [3H]-taurocholate and 10 uM cold taurocholate to room temperature HBSSH. A separate washing buffer was prepared by adding 10 uM cold taurocholate to HBSSH (30 ml per assay plate) and placed on ice. Using 100% DMSO, 8 point, 3-fold dilution curves for each test compound was prepared starting at 200 uM. Similarly, an 8 point dose response curve was prepared of the control compound [(3R,5R)-3-butyl-3-ethyl-7,8-bis(methyloxy)-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (Brieaddy, L. E. WO9605188, 1996)] starting at 1.8 mM. Drug plates were created by adding 3 uL of each concentration to a v-bottom 96-well plate then diluted 60-fold with 177 uL of assay buffer. Plates were removed from the incubator and allowed to cool to ambient temperature.
Measurement: IC50 = 504 nM (pChEMBL 6.300000190734863)
Descriptors: MW 486.68, ALogP 4.57, HBA 5, HBD 2, PSA 84.5, QED 0.51