lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(Nc1cnccc1C(=O)N1CCCC1CO)c1nc(C2CC2)ccc1Nc1cncnc1
InChIKey: VEMZGUGOZQUIQO-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 104.9 nM (pChEMBL 6.980000019073486)
Descriptors: MW 459.51, ALogP 2.74, HBA 8, HBD 3, PSA 133.23, QED 0.49
Compound (SMILES): CNC(=O)c1nn(C)cc1NC(=O)c1nc(CC(C)C)ncc1Nc1cncnc1
InChIKey: DGUCDTAFBARNOC-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 409.45, ALogP 1.55, HBA 9, HBD 3, PSA 139.61, QED 0.53
Compound (SMILES): CNC(=O)c1c(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)cnn1C
InChIKey: WCFFGYGVMUTILN-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 14.4 nM (pChEMBL 7.840000152587891)
Descriptors: MW 393.41, ALogP 1.23, HBA 9, HBD 3, PSA 139.61, QED 0.57
Compound (SMILES): CN(CC(C)(C)O)C(=O)c1ncccc1NC(=O)c1nc(C2CC2)cnc1Nc1cncnc1
InChIKey: YGKLHWAWQXXSEY-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 462.51, ALogP 2.38, HBA 9, HBD 3, PSA 146.12, QED 0.46
Compound (SMILES): CNC(=O)c1c(NC(=O)c2nc(C(C)C)cnc2Nc2cncnc2)cnn1C
InChIKey: DNPZBRPQZBCAFD-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 12.8 nM (pChEMBL 7.889999866485596)
Descriptors: MW 395.43, ALogP 1.48, HBA 9, HBD 3, PSA 139.61, QED 0.57
Compound (SMILES): Cn1ncc(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)c1C(=O)NCC(F)F
InChIKey: XMONCOJFWGVHSS-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 443.42, ALogP 1.87, HBA 9, HBD 3, PSA 139.61, QED 0.48
Compound (SMILES): NC1C=C(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)CCC1
InChIKey: VWDOGNVHWKGFOS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 392 nM (pChEMBL 6.409999847412109)
Descriptors: MW 429.47, ALogP 5.61, HBA 5, HBD 2, PSA 76.72, QED 0.44
Compound (SMILES): N[C@@H]1CN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)CC[C@@H]1O
InChIKey: WAISNUDWNYJNMT-UTKZUKDTSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 448.48, ALogP 3.61, HBA 7, HBD 3, PSA 100.19, QED 0.44
Compound (SMILES): N[C@@H]1CN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)CC[C@H]1O
InChIKey: WAISNUDWNYJNMT-DYESRHJHSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 448.48, ALogP 3.61, HBA 7, HBD 3, PSA 100.19, QED 0.44
Compound (SMILES): N[C@H]1C[C@@H](O)CN(c2ccncc2Nc2cccc3ccc(-c4c(F)cccc4F)nc23)C1
InChIKey: HXHFVYQPJRIKLE-DLBZAZTESA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 512 nM (pChEMBL 6.289999961853027)
Descriptors: MW 447.49, ALogP 4.22, HBA 6, HBD 3, PSA 87.3, QED 0.43
Compound (SMILES): N[C@H]1C[C@@H](CO)CN(c2ccncc2Nc2cccc3ccc(-c4c(F)cccc4F)nc23)C1
InChIKey: JEYMTHFRFGDBSF-AEFFLSMTSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 286 nM (pChEMBL 6.539999961853027)
Descriptors: MW 461.52, ALogP 4.46, HBA 6, HBD 3, PSA 87.3, QED 0.41
Compound (SMILES): CCO[C@@H]1C[C@H](N)CN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)C1
InChIKey: QEPUHWQDZRVJLO-ZWKOTPCHSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 476.53, ALogP 4.66, HBA 7, HBD 2, PSA 89.19, QED 0.42
Compound (SMILES): N[C@@H]1CCCN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)C1
InChIKey: BMYXNSDMYMRNAW-MRXNPFEDSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 432.48, ALogP 4.64, HBA 6, HBD 2, PSA 79.96, QED 0.49
Compound (SMILES): NC1CC(N)CN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)C1
InChIKey: HQICZWRMSXLUFU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 447.49, ALogP 3.58, HBA 7, HBD 3, PSA 105.98, QED 0.44
Compound (SMILES): N[C@@H]1CN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)CC[C@H]1F
InChIKey: CJCNVDWBDYXQMZ-CRAIPNDOSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 498 nM (pChEMBL 6.300000190734863)
Descriptors: MW 450.47, ALogP 4.59, HBA 6, HBD 2, PSA 79.96, QED 0.47
Compound (SMILES): N[C@H]1CN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)CC[C@@H]1F
InChIKey: CJCNVDWBDYXQMZ-YJBOKZPZSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 450.47, ALogP 4.59, HBA 6, HBD 2, PSA 79.96, QED 0.47
Compound (SMILES): NC1CCCCN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)C1
InChIKey: WNRDIKVAZGENRX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 446.51, ALogP 5.03, HBA 6, HBD 2, PSA 79.96, QED 0.46
Compound (SMILES): N[C@H]1CCCN(c2ncncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)C1
InChIKey: XPBFQTIASOFUJQ-HNNXBMFYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 433.47, ALogP 4.04, HBA 7, HBD 2, PSA 92.85, QED 0.5
Compound (SMILES): N[C@H]1C[C@@H](CF)CN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)C1
InChIKey: JLQSMFNIARXKCU-RDJZCZTQSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 464.5, ALogP 4.84, HBA 6, HBD 2, PSA 79.96, QED 0.44
Compound (SMILES): C[C@H]1C[C@@H](N)CN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)C1
InChIKey: ODHWZXUUXOFUQZ-DOTOQJQBSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 852 nM (pChEMBL 6.070000171661377)
Descriptors: MW 446.51, ALogP 4.89, HBA 6, HBD 2, PSA 79.96, QED 0.46
Compound (SMILES): C[C@@H]1C[C@H](N)CN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)C1
InChIKey: ODHWZXUUXOFUQZ-WBVHZDCISA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 446.51, ALogP 4.89, HBA 6, HBD 2, PSA 79.96, QED 0.46
Compound (SMILES): NC1CCCN(c2ccncc2Nc2cccc3cnc(-c4nccs4)nc23)C1
InChIKey: OAYLGJMFKMEJKI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 403.52, ALogP 3.82, HBA 8, HBD 2, PSA 92.85, QED 0.53
Compound (SMILES): N[C@H]1CCCN(c2ccncc2Nc2cccc3cnc(-c4c(F)cccc4F)nc23)C1
InChIKey: BMYXNSDMYMRNAW-INIZCTEOSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 432.48, ALogP 4.64, HBA 6, HBD 2, PSA 79.96, QED 0.49
Compound (SMILES): N[C@H]1CCCN(c2ccncc2Nc2cccc3cnc(-c4ccccc4F)nc23)C1
InChIKey: AJEKKBSRNRYYET-KRWDZBQOSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 131 nM (pChEMBL 6.880000114440918)
Descriptors: MW 414.49, ALogP 4.5, HBA 6, HBD 2, PSA 79.96, QED 0.51
Compound (SMILES): N[C@H]1CCCN(c2ccncc2Nc2cccc3cnc(-c4cccc(-c5nccs5)c4)nc23)C1
InChIKey: JZBBTWBWAAABLO-NRFANRHFSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: ATP Depletion Assay: The activity of PIM2 is measured using a luciferase-luciferin based ATP detection reagent to quantify ATP depletion resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed into white 384-well plates at 0.5 ul per well. To start the reaction, 10 ul of 10 nM Pim2 kinase and 20 uM BAD peptide (RSRHSSYPAGT-OH) in assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.05% BSA) is added into each well. After 15 minutes, 10 ul of 8 uM ATP in assay buffer is added. Final assay concentrations are 5 nM PIM2, 4 uM ATP, 10 uM BAD peptide and 2.5% DMSO. The reaction is performed until approximately 50% of the ATP is depleted, then stopped with the addition of 20 ul KinaseGlo Plus (Promega Corporation) solution. The stopped reaction is incubated for 10 minutes and the remaining ATP detected via luminescence on the Victor2 (Perkin Elmer).
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 479.61, ALogP 5.49, HBA 8, HBD 2, PSA 92.85, QED 0.34
Compound (SMILES): [C-]#[N+]C1C(C)=NC2=C(C(=O)OC2)C1c1ccc2n[nH]c(C)c2c1
InChIKey: ZPJBJFQOAIBECC-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Homogeneous Time-Resolved Fluorescence Assay: For the assay, 50 mL of a 100-fold concentrated solution of the test compound in DMSO is pipetted into a black low-volume 384-well microtiter plate (Greiner Bio-One, Frickenhausen, Germany). 2 uL of a solution of c-Met in assay buffer [25 mM Hepes/NaOH, pH 7.5; 5 mM MgCl2; 5 mM MnCl2; 2 mM dithiothreitol; 0.1% (v/v) Tween 20 (Sigma); 0.1% (w/v) bovine serum albumin] are added, and the mixture is incubated for 15 min at 22 C. to allow pre-binding of the test compound to the enzyme before the start of the kinase reaction. Then, the kinase reaction is started by the addition of 3 uL of a solution of adenosine triphosphate (ATP, 16.7 uM; final concentration in the 5 uL assay volume is 10 uM) and substrate (2.27 ug/mL, final concentration in the 5 uL assay volume is 1.36 ug/mL 30 nM) in assay buffer, and the resulting mixture is incubated for a reaction time of 30 min at 22 C.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 306.33, ALogP 2.53, HBA 4, HBD 1, PSA 71.7, QED 0.65
Compound (SMILES): [C-]#[N+]C1C(C)=NC2=C(C(=O)NC2)C1c1ccc2n[nH]c(C)c2c1
InChIKey: PYYVVGWOCLORHM-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Homogeneous Time-Resolved Fluorescence Assay: For the assay, 50 mL of a 100-fold concentrated solution of the test compound in DMSO is pipetted into a black low-volume 384-well microtiter plate (Greiner Bio-One, Frickenhausen, Germany). 2 uL of a solution of c-Met in assay buffer [25 mM Hepes/NaOH, pH 7.5; 5 mM MgCl2; 5 mM MnCl2; 2 mM dithiothreitol; 0.1% (v/v) Tween 20 (Sigma); 0.1% (w/v) bovine serum albumin] are added, and the mixture is incubated for 15 min at 22 C. to allow pre-binding of the test compound to the enzyme before the start of the kinase reaction. Then, the kinase reaction is started by the addition of 3 uL of a solution of adenosine triphosphate (ATP, 16.7 uM; final concentration in the 5 uL assay volume is 10 uM) and substrate (2.27 ug/mL, final concentration in the 5 uL assay volume is 1.36 ug/mL 30 nM) in assay buffer, and the resulting mixture is incubated for a reaction time of 30 min at 22 C.
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 305.34, ALogP 2.1, HBA 3, HBD 2, PSA 74.5, QED 0.79
Compound (SMILES): [C-]#[N+]C1=C2COCCN2C2=C(C(=O)OC2)C1c1ccc2[nH]nc(C)c2c1
InChIKey: RWVZNAHDKKVNTP-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Homogeneous Time-Resolved Fluorescence Assay: For the assay, 50 mL of a 100-fold concentrated solution of the test compound in DMSO is pipetted into a black low-volume 384-well microtiter plate (Greiner Bio-One, Frickenhausen, Germany). 2 uL of a solution of c-Met in assay buffer [25 mM Hepes/NaOH, pH 7.5; 5 mM MgCl2; 5 mM MnCl2; 2 mM dithiothreitol; 0.1% (v/v) Tween 20 (Sigma); 0.1% (w/v) bovine serum albumin] are added, and the mixture is incubated for 15 min at 22 C. to allow pre-binding of the test compound to the enzyme before the start of the kinase reaction. Then, the kinase reaction is started by the addition of 3 uL of a solution of adenosine triphosphate (ATP, 16.7 uM; final concentration in the 5 uL assay volume is 10 uM) and substrate (2.27 ug/mL, final concentration in the 5 uL assay volume is 1.36 ug/mL 30 nM) in assay buffer, and the resulting mixture is incubated for a reaction time of 30 min at 22 C.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 348.36, ALogP 2.24, HBA 5, HBD 1, PSA 71.81, QED 0.63
Compound (SMILES): [C-]#[N+]C1=C(C(F)(F)F)N=C2COC(=O)C2C1c1cc2c(C)n[nH]c2cc1F
InChIKey: AALHLPVAYBUAFB-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Homogeneous Time-Resolved Fluorescence Assay: For the assay, 50 mL of a 100-fold concentrated solution of the test compound in DMSO is pipetted into a black low-volume 384-well microtiter plate (Greiner Bio-One, Frickenhausen, Germany). 2 uL of a solution of c-Met in assay buffer [25 mM Hepes/NaOH, pH 7.5; 5 mM MgCl2; 5 mM MnCl2; 2 mM dithiothreitol; 0.1% (v/v) Tween 20 (Sigma); 0.1% (w/v) bovine serum albumin] are added, and the mixture is incubated for 15 min at 22 C. to allow pre-binding of the test compound to the enzyme before the start of the kinase reaction. Then, the kinase reaction is started by the addition of 3 uL of a solution of adenosine triphosphate (ATP, 16.7 uM; final concentration in the 5 uL assay volume is 10 uM) and substrate (2.27 ug/mL, final concentration in the 5 uL assay volume is 1.36 ug/mL 30 nM) in assay buffer, and the resulting mixture is incubated for a reaction time of 30 min at 22 C.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 378.29, ALogP 3.41, HBA 4, HBD 1, PSA 71.7, QED 0.47
Compound (SMILES): CCC(C)OC(=O)N1C[C@@H](N(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ncc(-c3cnn(C)c3)cn2)C[C@H]1CC
InChIKey: SMKZRYUCORUOAE-ZCWDRPESSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: In Vitro Assay: CETP Activity Kit (#RB-RPAK) was purchased from Roar Biochemical, Inc. (New York, N.Y., USA). To each well of a 96-well NBS half-area plate (costar #3686), 1.2 ng/well of the donor solution, 1 uL of the acceptor solution and 5 uL compound solution diluted in 100% DMSO were added in a 38 uL of buffer containing 10 mM Tris, 150 mM NaCl and 2 mM EDTA, pH 7.4. Then, the plate was sealed with Themowell Sealers (costar #6524) and followed by a mixing on a plate shaker by MICROPLATE MIXER MPX-96 (IWAKI) at power 3 for 10 sec at room temperature. After 10-min incubation at 37C., the reaction was started by adding 5 uL of rhCETP solution (Cardiovascular Target, New York, N.Y., USA) and mixed on the plate shaker for 10 sec, then the fluorescence intensity at 0 min was measured by a ARVO SX (Perkin Elmerr, USA) at excitation wavelength of 465 nm and emission wavelength of 535 nm. After 120 min-incubation at 37C., fluorescence intensity was measured again.
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 598.59, ALogP 6.71, HBA 7, HBD 0, PSA 76.38, QED 0.27
Compound (SMILES): Cc1cc(Nc2nccc(C)n2)cc(-c2cnc([C@@]3(O)CC[C@H](C(=O)O)C(C)(C)C3)s2)c1
InChIKey: OYKPWSZSBLRRPL-HOYKHHGWSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Invitrogen kinase assay (SRC)
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 452.58, ALogP 5.06, HBA 7, HBD 3, PSA 108.23, QED 0.5
Compound (SMILES): CC1(C(=O)O)CCC(O)(c2ncc(-c3cccc(Nc4nccc(C(F)(F)F)n4)c3)s2)CC1
InChIKey: DSBKXUBJVRREDE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Homogeneous Time-Resolved Fluorescence (HTRF) Assay : A recombinant GST-hSYK fusion protein was used to measure potency of compounds to inhibit human SYK activity. The recombinant human GST-SYK (Carna Biosciences #08-176) (5 pM final concentration) was incubated with various concentrations of the inhibitor diluted in DMSO (0.1% final concentration) for 10 minutes at room temperature in 15 mM Tris-HCl (pH 7.5), 0.01% tween 20, 2 mM DTT in 384 well plate format. To initiate the reaction the biotinylated substrate peptide (250 nM final concentration) that contains the phosphorylation site for SYK was added with magnesium (5 mM final concentration) and ATP (25 μM final concentration). Final volume of the reaction was 10 μL. Phosphorylation of the peptide was allowed to proceed for 45′ at room temperature.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 478.5, ALogP 5.22, HBA 7, HBD 3, PSA 108.23, QED 0.46
Compound (SMILES): Cc1cc(Nc2nccc(C(F)(F)F)n2)cc(-c2cnc([C@@]3(O)CC[C@H](C(=O)O)[C@H](C)C3)s2)c1
InChIKey: WZLQCTNWBQINDW-JFUMZLFPSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Homogeneous Time-Resolved Fluorescence (HTRF) Assay : A recombinant GST-hSYK fusion protein was used to measure potency of compounds to inhibit human SYK activity. The recombinant human GST-SYK (Carna Biosciences #08-176) (5 pM final concentration) was incubated with various concentrations of the inhibitor diluted in DMSO (0.1% final concentration) for 10 minutes at room temperature in 15 mM Tris-HCl (pH 7.5), 0.01% tween 20, 2 mM DTT in 384 well plate format. To initiate the reaction the biotinylated substrate peptide (250 nM final concentration) that contains the phosphorylation site for SYK was added with magnesium (5 mM final concentration) and ATP (25 μM final concentration). Final volume of the reaction was 10 μL. Phosphorylation of the peptide was allowed to proceed for 45′ at room temperature.
Measurement: IC50 < 0.5 nM (pChEMBL 9.300999641418457)
Descriptors: MW 492.52, ALogP 5.38, HBA 7, HBD 3, PSA 108.23, QED 0.44
Compound (SMILES): CC1CCN(c2nc(C(F)(F)F)ccc2CNC(=O)C(C)c2cc(O)c([N+](=O)[O-])c(F)c2)CC1
InChIKey: QDOHXPNPQLVMTN-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: FLIPR Assay: The FLIPR protocol consists of two substance additions. Initially, the compounds to be tested (10 uM) are pipeted onto the cells and the Ca2+ influx is compared with the control (capsaicin 10 uM). Information is gained therefrom in percentage activation relative to the Ca2+ signal after addition of 10 uM of capsaicin (CP). After incubation for 5 minutes, 100 nM of capsaicin are applied and the influx of Ca2+ is likewise determined. Desensitizing agonists and antagonists lead to suppression of the Ca2+ influx. The percentage inhibition is calculated in comparison with the maximum inhibition achieved with 10 uM of capsaicin.
Measurement: Ki = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 484.45, ALogP 4.51, HBA 6, HBD 2, PSA 108.6, QED 0.35
Compound (SMILES): Cc1c(CC(=O)O)cnn1Cc1ccc(NC(=O)c2ccc3ccccc3c2)cc1
InChIKey: BTCQMHUXQZGGHI-UHFFFAOYSA-N
Target: Prostaglandin D2 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y4
Assay: Radioligand Binding Assay: The CRTH2 receptor binding assay is performed in a scintillation proximity assay (SPA) format with the radioligand [3H]-PGD2 (Perkin Elmer, NET616000MC). CHO-K1-hCRTH2 cell membranes are again homogenized by passing through a single use needle (Terumo, 23Gx1'') and diluted in SPA incubation buffer in suitable concentrations (0.5-10 ug protein/well). The SPA assay is set up in 96 well microtiter plates (Perkin Elmer, CatNo. 6005040) in SPA incubation buffer with a final volume of 200 ul per well and final concentration of 50 mM Tris-HCl, 10 mM MgCl2, 150 mM NaCl, 1 mM EDTA pH 7.4, 0.1% bovine serum albumin). The SPA assay mixture contains 60 ul of the membrane suspension, 80 ul of Wheat Germ Agglutinin coated PVT beads (GE Healthcare, RPNQ-0001, 0.3 mg/well), 40 ul of [3H]-PGD2 diluted in SPA buffer to a final concentration of 1 nM (50 000 dpm) and 20 ul of the test compound (dissolved in dimethylsulfoxid).
Measurement: Ki = 24.6 nM (pChEMBL 7.610000133514404)
Descriptors: MW 399.45, ALogP 4.27, HBA 4, HBD 2, PSA 84.22, QED 0.51
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4nnc(C5CCCO5)s4)ccn23)c1
InChIKey: AJNWCFOYJHPQFV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 45.1 nM (pChEMBL 7.349999904632568)
Descriptors: MW 488.5, ALogP 5.06, HBA 7, HBD 2, PSA 93.44, QED 0.41
Compound (SMILES): CCOC(=O)C(C)(C)n1cc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)cn1
InChIKey: TXNNORIVSOVTRM-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 514.51, ALogP 4.85, HBA 7, HBD 2, PSA 102.55, QED 0.34
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4ccccn4)ccn23)c1
InChIKey: KPVANHBTOHTGQY-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 411.39, ALogP 4.75, HBA 4, HBD 2, PSA 71.32, QED 0.51
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4cnn(C5CCNCC5)c4)ccn23)c1
InChIKey: VWHPBSPJZJUNFB-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 483.5, ALogP 4.47, HBA 6, HBD 3, PSA 88.28, QED 0.39
Compound (SMILES): CC(C)(C(=O)O)n1cc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)cn1
InChIKey: KMLOPXDUQAYXNF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 66.9 nM (pChEMBL 7.170000076293945)
Descriptors: MW 486.45, ALogP 4.37, HBA 6, HBD 3, PSA 113.55, QED 0.37