lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCC(=O)N1C[C@H]2C[C@@H](Nc3c(C(N)=O)cnn4cc(-c5ccc(F)nc5)cc34)[C@H](C)[C@H]2C1
InChIKey: GOGAPLINTFESOO-ZQNRLITLSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Kinase Assay: The assay reactions were performed in U-bottom 384-well plates. The final assay volume was 30 ul prepared from 15 ul additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2,25 mM beta-glycerol phosphate 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of GST-JAK3 enzyme with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 ul of 35 mM EDTA to each sample. Each reaction mixture was analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison with no enzyme control reactions for 100% inhibition, and vehicle-only treated reactions for 0% inhibition. The final concentration of reagents in the assay was: ATP, 8 uM; fluoresceinated peptide, 1.5 uM.
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 450.52, ALogP 2.94, HBA 6, HBD 2, PSA 105.62, QED 0.58
Compound (SMILES): CC1(C)CN(c2ccc(C#N)cn2)CC[C@H]1Nc1c(C(N)=O)cnn2cc(N3CC[C@@H](O)C3=O)cc12
InChIKey: NYZHGLUYPINXHK-WOJBJXKFSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Kinase Assay: The assay reactions were performed in U-bottom 384-well plates. The final assay volume was 30 ul prepared from 15 ul additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2,25 mM beta-glycerol phosphate 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of GST-JAK3 enzyme with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 ul of 35 mM EDTA to each sample. Each reaction mixture was analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison with no enzyme control reactions for 100% inhibition, and vehicle-only treated reactions for 0% inhibition. The final concentration of reagents in the assay was: ATP, 8 uM; fluoresceinated peptide, 1.5 uM.
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 488.55, ALogP 1.51, HBA 9, HBD 3, PSA 152.88, QED 0.49
Compound (SMILES): CC1(C)CN(c2ccc(C#N)cn2)CC[C@H]1Nc1c(C(N)=O)cnn2cc(N3CC(c4ccccc4)CC3=O)cc12
InChIKey: GLRTWPVXHQIDTC-ZWAGFTRDSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Kinase Assay: The assay reactions were performed in U-bottom 384-well plates. The final assay volume was 30 ul prepared from 15 ul additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2,25 mM beta-glycerol phosphate 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of GST-JAK3 enzyme with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 ul of 35 mM EDTA to each sample. Each reaction mixture was analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison with no enzyme control reactions for 100% inhibition, and vehicle-only treated reactions for 0% inhibition. The final concentration of reagents in the assay was: ATP, 8 uM; fluoresceinated peptide, 1.5 uM.
Measurement: IC50 = 11.4 nM (pChEMBL 7.940000057220459)
Descriptors: MW 548.65, ALogP 3.94, HBA 8, HBD 2, PSA 132.65, QED 0.37
Compound (SMILES): CC1(C)CN(c2ncc(C#N)cn2)CC[C@H]1Nc1c(C(N)=O)cnn2cc(N3CCC(CCCC(=O)O)C3=O)cc12
InChIKey: KQTMBQOVTYUNAC-LMNIDFBRSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Kinase Assay: The assay reactions were performed in U-bottom 384-well plates. The final assay volume was 30 ul prepared from 15 ul additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2,25 mM beta-glycerol phosphate 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of GST-JAK3 enzyme with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 ul of 35 mM EDTA to each sample. Each reaction mixture was analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison with no enzyme control reactions for 100% inhibition, and vehicle-only treated reactions for 0% inhibition. The final concentration of reagents in the assay was: ATP, 8 uM; fluoresceinated peptide, 1.5 uM.
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 559.63, ALogP 2.42, HBA 10, HBD 3, PSA 182.84, QED 0.35
Compound (SMILES): CC[C@@H]1CN(S(C)(=O)=O)CC[C@H]1Nc1c(C(N)=O)cnn2cc(-c3cnn(CCC#N)c3)cc12
InChIKey: YDBAZCZNEPOFIH-DNVCBOLYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Kinase Assay: The assay reactions were performed in U-bottom 384-well plates. The final assay volume was 30 ul prepared from 15 ul additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2,25 mM beta-glycerol phosphate 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of GST-JAK3 enzyme with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 ul of 35 mM EDTA to each sample. Each reaction mixture was analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison with no enzyme control reactions for 100% inhibition, and vehicle-only treated reactions for 0% inhibition. The final concentration of reagents in the assay was: ATP, 8 uM; fluoresceinated peptide, 1.5 uM.
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 484.59, ALogP 1.68, HBA 9, HBD 2, PSA 151.41, QED 0.49
Compound (SMILES): CC[C@@H]1CN(C(=O)[C@@H](O)CC)CC[C@H]1Nc1c(C(N)=O)cnn2cc(-c3cnn(C)c3)cc12
InChIKey: VWAHLTNZWKHTHS-DJKXOVBDSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Kinase Assay: The assay reactions were performed in U-bottom 384-well plates. The final assay volume was 30 ul prepared from 15 ul additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2,25 mM beta-glycerol phosphate 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of GST-JAK3 enzyme with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 ul of 35 mM EDTA to each sample. Each reaction mixture was analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison with no enzyme control reactions for 100% inhibition, and vehicle-only treated reactions for 0% inhibition. The final concentration of reagents in the assay was: ATP, 8 uM; fluoresceinated peptide, 1.5 uM.
Measurement: IC50 = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 453.55, ALogP 1.64, HBA 8, HBD 3, PSA 130.78, QED 0.5
Compound (SMILES): CC[C@@H]1CN(C(=O)C(C)(C)O)CC[C@H]1Nc1c(C(N)=O)cnn2cc(-c3ccnc(C)c3)cc12
InChIKey: IADNRIHGYPSXNX-OXQOHEQNSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Kinase Assay: The assay reactions were performed in U-bottom 384-well plates. The final assay volume was 30 ul prepared from 15 ul additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2,25 mM beta-glycerol phosphate 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of GST-JAK3 enzyme with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 ul of 35 mM EDTA to each sample. Each reaction mixture was analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison with no enzyme control reactions for 100% inhibition, and vehicle-only treated reactions for 0% inhibition. The final concentration of reagents in the assay was: ATP, 8 uM; fluoresceinated peptide, 1.5 uM.
Measurement: IC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 464.57, ALogP 2.61, HBA 7, HBD 3, PSA 125.85, QED 0.51
Compound (SMILES): CC[C@@H]1CN(C(=O)[C@H](C)O)CC[C@H]1Nc1c(C(N)=O)cnn2cc(-c3ccnc(OC)c3)cc12
InChIKey: LBJMTUJAVUTGFB-QMTMVMCOSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Kinase Assay: The assay reactions were performed in U-bottom 384-well plates. The final assay volume was 30 ul prepared from 15 ul additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2,25 mM beta-glycerol phosphate 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of GST-JAK3 enzyme with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 ul of 35 mM EDTA to each sample. Each reaction mixture was analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison with no enzyme control reactions for 100% inhibition, and vehicle-only treated reactions for 0% inhibition. The final concentration of reagents in the assay was: ATP, 8 uM; fluoresceinated peptide, 1.5 uM.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 466.54, ALogP 1.92, HBA 8, HBD 3, PSA 135.08, QED 0.48
Compound (SMILES): CC[C@@H]1CN(C(=O)[C@H](C)O)CC[C@H]1Nc1c(C(N)=O)cnn2cc(-c3cnn(CC(C)C)c3)cc12
InChIKey: VFWRNEZRIMLXRO-CSODHUTKSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Kinase Assay: The assay reactions were performed in U-bottom 384-well plates. The final assay volume was 30 ul prepared from 15 ul additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2,25 mM beta-glycerol phosphate 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of GST-JAK3 enzyme with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 ul of 35 mM EDTA to each sample. Each reaction mixture was analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison with no enzyme control reactions for 100% inhibition, and vehicle-only treated reactions for 0% inhibition. The final concentration of reagents in the assay was: ATP, 8 uM; fluoresceinated peptide, 1.5 uM.
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 481.6, ALogP 2.37, HBA 8, HBD 3, PSA 130.78, QED 0.45
Compound (SMILES): CC[C@@H]1CN(C(=O)CC(F)(F)F)CC[C@H]1Nc1c(C(N)=O)cnn2cc(-c3cnn(C)c3)cc12
InChIKey: CSWQAXHAVSQGGL-CXAGYDPISA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Kinase Assay: The assay reactions were performed in U-bottom 384-well plates. The final assay volume was 30 ul prepared from 15 ul additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2,25 mM beta-glycerol phosphate 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of GST-JAK3 enzyme with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 ul of 35 mM EDTA to each sample. Each reaction mixture was analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison with no enzyme control reactions for 100% inhibition, and vehicle-only treated reactions for 0% inhibition. The final concentration of reagents in the assay was: ATP, 8 uM; fluoresceinated peptide, 1.5 uM.
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 477.49, ALogP 2.83, HBA 7, HBD 2, PSA 110.55, QED 0.57
Compound (SMILES): C[C@@H]1CN(C(=O)N2Cc3c(NC(=O)c4ccc(Cl)cn4)n[nH]c3C2(C)C)[C@@H](C)CN1C1CCOCC1
InChIKey: OJSMHIUSRXNYIB-CVEARBPZSA-N
Target: Protein kinase C beta type (SINGLE PROTEIN), Homo sapiens
UniProt: P05771
Assay: Inhibition Assay: Protein Kinase C beta 2 (PKC beta II) catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the PKC Pseudosubstrate peptide (A->S, RFARKGSLRQKNV). This transfer is coupled to the oxidation of p-NADH through the activities of Pyruvate Kinase (PK) and Lactate Dehydrogenase (LDH). (3-NADH conversion to NAD+ is monitored by the decrease in absorbance at 340 nm (e=6.22 cm-1 mM-1) using a Molecular Devices SPECTRA max PLUS spectrophotometer.A typical assay was carried out on a 96-well, clear microtiter plate in a Molecular Devices spectrophotometer for 20 minutes at 30 C. in 0.1 mL of assay buffer containing 50 mM HEPES, pH 7.4, 5 nM PKC, 23 units of pyruvate kinase, 33 units of lactate dehydrogenase, 0.15 mM peptide, 0.1 mM ATP, 1 mM DTT, 4 mM PEP, 8 mM MgCl2, 0.3 mM NADH, 60 mM CaCl2, 10 mg/mL PS, 50 ng/mL PMA, 7.5% DMSO and from about 10,000 nM to 0.169 nM compound inhibitor.
Measurement: Ki < 10 nM (pChEMBL 8)
Descriptors: MW 516.05, ALogP 3.45, HBA 6, HBD 2, PSA 106.69, QED 0.65
Compound (SMILES): C[C@@H]1CN(C(=O)N2Cc3c(NC(=O)c4cnccn4)n[nH]c3C2(C)C)[C@@H](C)CN1CC1CCOCC1
InChIKey: RBAJTZRKAYVXGN-SJORKVTESA-N
Target: Protein kinase C beta type (SINGLE PROTEIN), Homo sapiens
UniProt: P05771
Assay: Inhibition Assay: Protein Kinase C beta 2 (PKC beta II) catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the PKC Pseudosubstrate peptide (A->S, RFARKGSLRQKNV). This transfer is coupled to the oxidation of p-NADH through the activities of Pyruvate Kinase (PK) and Lactate Dehydrogenase (LDH). (3-NADH conversion to NAD+ is monitored by the decrease in absorbance at 340 nm (e=6.22 cm-1 mM-1) using a Molecular Devices SPECTRA max PLUS spectrophotometer.A typical assay was carried out on a 96-well, clear microtiter plate in a Molecular Devices spectrophotometer for 20 minutes at 30 C. in 0.1 mL of assay buffer containing 50 mM HEPES, pH 7.4, 5 nM PKC, 23 units of pyruvate kinase, 33 units of lactate dehydrogenase, 0.15 mM peptide, 0.1 mM ATP, 1 mM DTT, 4 mM PEP, 8 mM MgCl2, 0.3 mM NADH, 60 mM CaCl2, 10 mg/mL PS, 50 ng/mL PMA, 7.5% DMSO and from about 10,000 nM to 0.169 nM compound inhibitor.
Measurement: Ki = 52.7 nM (pChEMBL 7.28000020980835)
Descriptors: MW 496.62, ALogP 2.44, HBA 7, HBD 2, PSA 119.58, QED 0.67
Compound (SMILES): C[C@@H]1CN(C(=O)N2Cc3c(NC(=O)c4ncccn4)n[nH]c3C2(C)C)[C@@H](C)CN1CC1CCOCC1
InChIKey: PFNDHSGBDBZRMM-SJORKVTESA-N
Target: Protein kinase C beta type (SINGLE PROTEIN), Homo sapiens
UniProt: P05771
Assay: Inhibition Assay: Protein Kinase C beta 2 (PKC beta II) catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the PKC Pseudosubstrate peptide (A->S, RFARKGSLRQKNV). This transfer is coupled to the oxidation of p-NADH through the activities of Pyruvate Kinase (PK) and Lactate Dehydrogenase (LDH). (3-NADH conversion to NAD+ is monitored by the decrease in absorbance at 340 nm (e=6.22 cm-1 mM-1) using a Molecular Devices SPECTRA max PLUS spectrophotometer.A typical assay was carried out on a 96-well, clear microtiter plate in a Molecular Devices spectrophotometer for 20 minutes at 30 C. in 0.1 mL of assay buffer containing 50 mM HEPES, pH 7.4, 5 nM PKC, 23 units of pyruvate kinase, 33 units of lactate dehydrogenase, 0.15 mM peptide, 0.1 mM ATP, 1 mM DTT, 4 mM PEP, 8 mM MgCl2, 0.3 mM NADH, 60 mM CaCl2, 10 mg/mL PS, 50 ng/mL PMA, 7.5% DMSO and from about 10,000 nM to 0.169 nM compound inhibitor.
Measurement: Ki = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 496.62, ALogP 2.44, HBA 7, HBD 2, PSA 119.58, QED 0.67
Compound (SMILES): Cc1noc(C)c1CC(=O)Nc1n[nH]c2c1CN(C(=O)N1C[C@@H](C)N(CC3CCOCC3)C[C@@H]1C)C2(C)C
InChIKey: MUALRCZUJQNJGX-SJORKVTESA-N
Target: Protein kinase C beta type (SINGLE PROTEIN), Homo sapiens
UniProt: P05771
Assay: Inhibition Assay: Protein Kinase C beta 2 (PKC beta II) catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the PKC Pseudosubstrate peptide (A->S, RFARKGSLRQKNV). This transfer is coupled to the oxidation of p-NADH through the activities of Pyruvate Kinase (PK) and Lactate Dehydrogenase (LDH). (3-NADH conversion to NAD+ is monitored by the decrease in absorbance at 340 nm (e=6.22 cm-1 mM-1) using a Molecular Devices SPECTRA max PLUS spectrophotometer.A typical assay was carried out on a 96-well, clear microtiter plate in a Molecular Devices spectrophotometer for 20 minutes at 30 C. in 0.1 mL of assay buffer containing 50 mM HEPES, pH 7.4, 5 nM PKC, 23 units of pyruvate kinase, 33 units of lactate dehydrogenase, 0.15 mM peptide, 0.1 mM ATP, 1 mM DTT, 4 mM PEP, 8 mM MgCl2, 0.3 mM NADH, 60 mM CaCl2, 10 mg/mL PS, 50 ng/mL PMA, 7.5% DMSO and from about 10,000 nM to 0.169 nM compound inhibitor.
Measurement: Ki = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 527.67, ALogP 3.19, HBA 7, HBD 2, PSA 119.83, QED 0.61
Compound (SMILES): C[C@@H]1CN(C(=O)N2Cc3c(NC(=O)c4ccc(C(F)(F)F)cn4)n[nH]c3C2(C)C)[C@@H](C)CN1CC1CCOCC1
InChIKey: KIDSAMBMXNPHKM-SJORKVTESA-N
Target: Protein kinase C beta type (SINGLE PROTEIN), Homo sapiens
UniProt: P05771
Assay: Inhibition Assay: Protein Kinase C beta 2 (PKC beta II) catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the PKC Pseudosubstrate peptide (A->S, RFARKGSLRQKNV). This transfer is coupled to the oxidation of p-NADH through the activities of Pyruvate Kinase (PK) and Lactate Dehydrogenase (LDH). (3-NADH conversion to NAD+ is monitored by the decrease in absorbance at 340 nm (e=6.22 cm-1 mM-1) using a Molecular Devices SPECTRA max PLUS spectrophotometer.A typical assay was carried out on a 96-well, clear microtiter plate in a Molecular Devices spectrophotometer for 20 minutes at 30 C. in 0.1 mL of assay buffer containing 50 mM HEPES, pH 7.4, 5 nM PKC, 23 units of pyruvate kinase, 33 units of lactate dehydrogenase, 0.15 mM peptide, 0.1 mM ATP, 1 mM DTT, 4 mM PEP, 8 mM MgCl2, 0.3 mM NADH, 60 mM CaCl2, 10 mg/mL PS, 50 ng/mL PMA, 7.5% DMSO and from about 10,000 nM to 0.169 nM compound inhibitor.
Measurement: Ki = 4.17 nM (pChEMBL 8.380000114440918)
Descriptors: MW 563.62, ALogP 4.07, HBA 6, HBD 2, PSA 106.69, QED 0.58
Compound (SMILES): C[C@@H]1CN(C(=O)N2Cc3c(NC(=O)c4ccc(C#N)cn4)n[nH]c3C2(C)C)[C@@H](C)CN1CC1CCOCC1
InChIKey: LJQVTEDWNZBUJS-MSOLQXFVSA-N
Target: Protein kinase C beta type (SINGLE PROTEIN), Homo sapiens
UniProt: P05771
Assay: Inhibition Assay: Protein Kinase C beta 2 (PKC beta II) catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the PKC Pseudosubstrate peptide (A->S, RFARKGSLRQKNV). This transfer is coupled to the oxidation of p-NADH through the activities of Pyruvate Kinase (PK) and Lactate Dehydrogenase (LDH). (3-NADH conversion to NAD+ is monitored by the decrease in absorbance at 340 nm (e=6.22 cm-1 mM-1) using a Molecular Devices SPECTRA max PLUS spectrophotometer.A typical assay was carried out on a 96-well, clear microtiter plate in a Molecular Devices spectrophotometer for 20 minutes at 30 C. in 0.1 mL of assay buffer containing 50 mM HEPES, pH 7.4, 5 nM PKC, 23 units of pyruvate kinase, 33 units of lactate dehydrogenase, 0.15 mM peptide, 0.1 mM ATP, 1 mM DTT, 4 mM PEP, 8 mM MgCl2, 0.3 mM NADH, 60 mM CaCl2, 10 mg/mL PS, 50 ng/mL PMA, 7.5% DMSO and from about 10,000 nM to 0.169 nM compound inhibitor.
Measurement: Ki < 10 nM (pChEMBL 8)
Descriptors: MW 520.64, ALogP 2.92, HBA 7, HBD 2, PSA 130.48, QED 0.63
Compound (SMILES): C[C@@H]1CN(C(=O)N2Cc3c(NC(=O)c4ccc(C#N)cn4)n[nH]c3C2(C)C)[C@@H](C)CN1C
InChIKey: XIYAWZAXLBXABX-KGLIPLIRSA-N
Target: Protein kinase C beta type (SINGLE PROTEIN), Homo sapiens
UniProt: P05771
Assay: Inhibition Assay: Protein Kinase C beta 2 (PKC beta II) catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the PKC Pseudosubstrate peptide (A->S, RFARKGSLRQKNV). This transfer is coupled to the oxidation of p-NADH through the activities of Pyruvate Kinase (PK) and Lactate Dehydrogenase (LDH). (3-NADH conversion to NAD+ is monitored by the decrease in absorbance at 340 nm (e=6.22 cm-1 mM-1) using a Molecular Devices SPECTRA max PLUS spectrophotometer.A typical assay was carried out on a 96-well, clear microtiter plate in a Molecular Devices spectrophotometer for 20 minutes at 30 C. in 0.1 mL of assay buffer containing 50 mM HEPES, pH 7.4, 5 nM PKC, 23 units of pyruvate kinase, 33 units of lactate dehydrogenase, 0.15 mM peptide, 0.1 mM ATP, 1 mM DTT, 4 mM PEP, 8 mM MgCl2, 0.3 mM NADH, 60 mM CaCl2, 10 mg/mL PS, 50 ng/mL PMA, 7.5% DMSO and from about 10,000 nM to 0.169 nM compound inhibitor.
Measurement: Ki = 28.7 nM (pChEMBL 7.539999961853027)
Descriptors: MW 436.52, ALogP 2.12, HBA 6, HBD 2, PSA 121.25, QED 0.74
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)c4cc(-c5ccccc5)on4)cc3F)c2cc1OC
InChIKey: XKHVSFYFKFKRAN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 485.47, ALogP 6.09, HBA 7, HBD 1, PSA 95.71, QED 0.3
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)c4ccco4)cc3)c2cc1OC
InChIKey: KFXSUBJQTMUSBF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 390.4, ALogP 4.89, HBA 6, HBD 1, PSA 82.82, QED 0.5
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)c4ccsc4)cc3)c2cc1OC
InChIKey: BYHCUHXSYIASPR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 = 7042 nM (pChEMBL 5.150000095367432)
Descriptors: MW 406.46, ALogP 5.36, HBA 6, HBD 1, PSA 69.68, QED 0.47
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)c4ccncc4)cc3)c2cc1OC
InChIKey: HGYFLRHYOSVLBP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 401.42, ALogP 4.69, HBA 6, HBD 1, PSA 82.57, QED 0.5
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)c4cccs4)cc3)c2cc1OC
InChIKey: PJGCXNNYOCGEQN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 = 8293 nM (pChEMBL 5.079999923706055)
Descriptors: MW 406.46, ALogP 5.36, HBA 6, HBD 1, PSA 69.68, QED 0.47
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)c4ccccn4)cc3)c2cc1OC
InChIKey: NJOJKCSNOKXOJE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 = 9302 nM (pChEMBL 5.03000020980835)
Descriptors: MW 401.42, ALogP 4.69, HBA 6, HBD 1, PSA 82.57, QED 0.5
Compound (SMILES): COc1cc2nccc(Oc3ccc(N)cc3F)c2cc1OC
InChIKey: SIDZXXQYQLBOHZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 314.32, ALogP 3.77, HBA 5, HBD 1, PSA 66.6, QED 0.74
Compound (SMILES): COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
InChIKey: VXEQRXJATQUJSN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 296.33, ALogP 3.63, HBA 5, HBD 1, PSA 66.6, QED 0.74
Compound (SMILES): COc1cc2nccc(Oc3ccc(N)cc3C)c2cc1OC
InChIKey: UOZCXYMRQHMNRC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 310.35, ALogP 3.93, HBA 5, HBD 1, PSA 66.6, QED 0.74
Compound (SMILES): COc1cc2nccc(Oc3ccc(N)cc3Cl)c2cc1OC
InChIKey: DCFZOECVVBSZLL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 330.77, ALogP 4.28, HBA 5, HBD 1, PSA 66.6, QED 0.72
Compound (SMILES): COc1cc(Oc2ccnc3cc(OC)c(OC)cc23)ccc1N
InChIKey: VKTFYWFVBORGFY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 326.35, ALogP 3.64, HBA 6, HBD 1, PSA 75.83, QED 0.72
Compound (SMILES): COc1cc2nccc(Oc3ccc(N)c(C)c3)c2cc1OC
InChIKey: BXVUWRXAXZVIOJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 310.35, ALogP 3.93, HBA 5, HBD 1, PSA 66.6, QED 0.74
Compound (SMILES): COc1cc2c(Oc3ccc(N)cc3F)ccnc2cc1OCCCN1CCOCC1
InChIKey: MVLNDUYPIKVWDO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 = 8503 nM (pChEMBL 5.070000171661377)
Descriptors: MW 427.48, ALogP 3.86, HBA 7, HBD 1, PSA 79.07, QED 0.43
Compound (SMILES): COc1cc2c(Oc3ccc(N)cc3F)ccnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1
InChIKey: HODLDQAFNUUMAJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Binding Assay: The principle behind this assay is based upon the binding and displacement of an Alexa Fluor 647-labeled tracer to the kinase of interest. Binding of the tracer to the kinase is detected using an EU-labeled anti-tag antibody. Simultaneous binding of both the tracer and antibody to the kinase gives rise to a FRET-signal. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET-signal. At first a compound according to formula (I) was diluted in 20 mM Hepes pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Next Axl kinase (5 nM final concentration; Proqinase), kinase tracer (15 nM final concentration; Invitrogen) and LanthaScreen Eu-Anti-GST antibody (2 nM final concentration; Invitrogen) was mixed with suitable compound dilutions and incubated for 1 hour. FRET-signal was quantified employing an EnVision Multilabelreader 2104 (Perkin Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 497.57, ALogP 5.78, HBA 7, HBD 1, PSA 96.14, QED 0.43
Compound (SMILES): Cc1cc(NC(=O)c2cnn3cccnc23)n(-c2cc(Cl)ccc2C)n1
InChIKey: MSQAEIWPJMSSTI-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 = 99.6 nM (pChEMBL 7)
Descriptors: MW 366.81, ALogP 3.44, HBA 6, HBD 1, PSA 77.11, QED 0.6
Compound (SMILES): Cc1cc(NC(=O)c2cnn3cccnc23)n(-c2cc(C#N)ccc2C)n1
InChIKey: IFTUJXXKLGWTIY-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 = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 357.38, ALogP 2.66, HBA 7, HBD 1, PSA 100.9, QED 0.61
Compound (SMILES): Cc1cc(NC(=O)c2cnn3cccnc23)n(-c2cc(Cl)ccc2Cl)n1
InChIKey: YHYZLBBGBXJVRK-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 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 387.23, ALogP 3.78, HBA 6, HBD 1, PSA 77.11, QED 0.58
Compound (SMILES): Cc1cc(NC(=O)c2cnn3cccnc23)n(-c2ccccc2Br)n1
InChIKey: OUDRBZOMWXKLSN-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 = 18 nM (pChEMBL 7.75)
Descriptors: MW 397.24, ALogP 3.24, HBA 6, HBD 1, PSA 77.11, QED 0.58
Compound (SMILES): O=C(Nc1ccnn1-c1ccccc1Cl)c1cnn2cccnc12
InChIKey: CHPDJDGBCILPAW-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 = 15.2 nM (pChEMBL 7.820000171661377)
Descriptors: MW 338.76, ALogP 2.82, HBA 6, HBD 1, PSA 77.11, QED 0.62
Compound (SMILES): O=C(Nc1ccnn1-c1ccc(Cl)cc1)c1cnn2cccnc12
InChIKey: SMVZAQMYQIIFKQ-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 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 338.76, ALogP 2.82, HBA 6, HBD 1, PSA 77.11, QED 0.62
Compound (SMILES): O=C(Nc1ccncc1-c1cccc(F)c1)c1cnn2cccnc12
InChIKey: OEIOCPLLBAECAL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase 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 = 153 nM (pChEMBL 6.820000171661377)
Descriptors: MW 333.33, ALogP 3.18, HBA 5, HBD 1, PSA 72.18, QED 0.62