lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(Cc1cccc(-c2cnc(N3Cc4cccnc4C3)nc2)c1)C(=O)CN
InChIKey: PFHNADXHZMQLMB-UHFFFAOYSA-N
Target: Amine oxidase [copper-containing] 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08590
Assay: Inhibition Assay: A rat VAP-enzyme 1 (SSAO) activity was measured by a radiochemistry-enzymatic assay using 14C-benzylamine as an artificial substrate. An enzyme suspension prepared from CHO (Chinese Hamster Ovary) cells stably expressing a rat VAP-enzyme 1 (SSAO) was preincubated with the compound of the present invention in a 96-well microplate at room temperature for 30 minutes. Subsequently, the enzyme suspension was incubated with 14C-benzylamine (a final concentration of 1×10−5 mol/L) to a final volume of 50 mL at 37° C. for 1 hour. The enzymatic reaction was stopped by the addition of 2 mol/L (50 μL) of citric acid. The oxidation products were extracted directly in a 200-μL toluene scintillator, and the radioactivity was measured with a scintillation spectrometer.
Measurement: IC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 374.45, ALogP 1.98, HBA 6, HBD 1, PSA 88.24, QED 0.73
Compound (SMILES): Cc1nc2c(s1)CN(c1ncc(-c3cccc(CN(C)C(=O)CN)c3)cn1)CC2
InChIKey: WAELLVNPVPWJLP-UHFFFAOYSA-N
Target: Amine oxidase [copper-containing] 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08590
Assay: Inhibition Assay: A rat VAP-enzyme 1 (SSAO) activity was measured by a radiochemistry-enzymatic assay using 14C-benzylamine as an artificial substrate. An enzyme suspension prepared from CHO (Chinese Hamster Ovary) cells stably expressing a rat VAP-enzyme 1 (SSAO) was preincubated with the compound of the present invention in a 96-well microplate at room temperature for 30 minutes. Subsequently, the enzyme suspension was incubated with 14C-benzylamine (a final concentration of 1×10−5 mol/L) to a final volume of 50 mL at 37° C. for 1 hour. The enzymatic reaction was stopped by the addition of 2 mol/L (50 μL) of citric acid. The oxidation products were extracted directly in a 200-μL toluene scintillator, and the radioactivity was measured with a scintillation spectrometer.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 408.53, ALogP 2.39, HBA 7, HBD 1, PSA 88.24, QED 0.7
Compound (SMILES): CN(Cc1cccc(-c2cnc(N3CCN(c4ncccc4Cl)CC3)nc2)c1)C(=O)CN
InChIKey: BBDPFGPPTUKKBZ-UHFFFAOYSA-N
Target: Amine oxidase [copper-containing] 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08590
Assay: Inhibition Assay: A rat VAP-enzyme 1 (SSAO) activity was measured by a radiochemistry-enzymatic assay using 14C-benzylamine as an artificial substrate. An enzyme suspension prepared from CHO (Chinese Hamster Ovary) cells stably expressing a rat VAP-enzyme 1 (SSAO) was preincubated with the compound of the present invention in a 96-well microplate at room temperature for 30 minutes. Subsequently, the enzyme suspension was incubated with 14C-benzylamine (a final concentration of 1×10−5 mol/L) to a final volume of 50 mL at 37° C. for 1 hour. The enzymatic reaction was stopped by the addition of 2 mol/L (50 μL) of citric acid. The oxidation products were extracted directly in a 200-μL toluene scintillator, and the radioactivity was measured with a scintillation spectrometer.
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 451.96, ALogP 2.44, HBA 7, HBD 1, PSA 91.48, QED 0.61
Compound (SMILES): CN(Cc1cccc(-c2cnc(N3CCC(c4cccnc4)CC3)nc2)c1)C(=O)CN
InChIKey: RAJBHCBHSBOWCA-UHFFFAOYSA-N
Target: Amine oxidase [copper-containing] 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08590
Assay: Inhibition Assay: A rat VAP-enzyme 1 (SSAO) activity was measured by a radiochemistry-enzymatic assay using 14C-benzylamine as an artificial substrate. An enzyme suspension prepared from CHO (Chinese Hamster Ovary) cells stably expressing a rat VAP-enzyme 1 (SSAO) was preincubated with the compound of the present invention in a 96-well microplate at room temperature for 30 minutes. Subsequently, the enzyme suspension was incubated with 14C-benzylamine (a final concentration of 1×10−5 mol/L) to a final volume of 50 mL at 37° C. for 1 hour. The enzymatic reaction was stopped by the addition of 2 mol/L (50 μL) of citric acid. The oxidation products were extracted directly in a 200-μL toluene scintillator, and the radioactivity was measured with a scintillation spectrometer.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 416.53, ALogP 2.84, HBA 6, HBD 1, PSA 88.24, QED 0.66
Compound (SMILES): CN(Cc1cccc(-c2cnc(N3CC=C(c4cccnc4)CC3)nc2)c1)C(=O)CN
InChIKey: HKPHKNCGPOEEFL-UHFFFAOYSA-N
Target: Amine oxidase [copper-containing] 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08590
Assay: Inhibition Assay: A rat VAP-enzyme 1 (SSAO) activity was measured by a radiochemistry-enzymatic assay using 14C-benzylamine as an artificial substrate. An enzyme suspension prepared from CHO (Chinese Hamster Ovary) cells stably expressing a rat VAP-enzyme 1 (SSAO) was preincubated with the compound of the present invention in a 96-well microplate at room temperature for 30 minutes. Subsequently, the enzyme suspension was incubated with 14C-benzylamine (a final concentration of 1×10−5 mol/L) to a final volume of 50 mL at 37° C. for 1 hour. The enzymatic reaction was stopped by the addition of 2 mol/L (50 μL) of citric acid. The oxidation products were extracted directly in a 200-μL toluene scintillator, and the radioactivity was measured with a scintillation spectrometer.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 414.51, ALogP 2.75, HBA 6, HBD 1, PSA 88.24, QED 0.67
Compound (SMILES): CN(Cc1cccc(-c2cnc(N3CCS(=O)(=O)CC3)nc2)c1)C(=O)CN
InChIKey: FREZDGCRHGKROQ-UHFFFAOYSA-N
Target: Amine oxidase [copper-containing] 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08590
Assay: Inhibition Assay: A rat VAP-enzyme 1 (SSAO) activity was measured by a radiochemistry-enzymatic assay using 14C-benzylamine as an artificial substrate. An enzyme suspension prepared from CHO (Chinese Hamster Ovary) cells stably expressing a rat VAP-enzyme 1 (SSAO) was preincubated with the compound of the present invention in a 96-well microplate at room temperature for 30 minutes. Subsequently, the enzyme suspension was incubated with 14C-benzylamine (a final concentration of 1×10−5 mol/L) to a final volume of 50 mL at 37° C. for 1 hour. The enzymatic reaction was stopped by the addition of 2 mol/L (50 μL) of citric acid. The oxidation products were extracted directly in a 200-μL toluene scintillator, and the radioactivity was measured with a scintillation spectrometer.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 389.48, ALogP 0.3, HBA 7, HBD 1, PSA 109.49, QED 0.78
Compound (SMILES): CN(Cc1cccc(-c2cnc(N3CCN(c4ccc(C#N)nc4)CC3)nc2)c1)C(=O)CN
InChIKey: XDABGJRXAMEIOF-UHFFFAOYSA-N
Target: Amine oxidase [copper-containing] 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08590
Assay: Inhibition Assay: A rat VAP-enzyme 1 (SSAO) activity was measured by a radiochemistry-enzymatic assay using 14C-benzylamine as an artificial substrate. An enzyme suspension prepared from CHO (Chinese Hamster Ovary) cells stably expressing a rat VAP-enzyme 1 (SSAO) was preincubated with the compound of the present invention in a 96-well microplate at room temperature for 30 minutes. Subsequently, the enzyme suspension was incubated with 14C-benzylamine (a final concentration of 1×10−5 mol/L) to a final volume of 50 mL at 37° C. for 1 hour. The enzymatic reaction was stopped by the addition of 2 mol/L (50 μL) of citric acid. The oxidation products were extracted directly in a 200-μL toluene scintillator, and the radioactivity was measured with a scintillation spectrometer.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 442.53, ALogP 1.65, HBA 8, HBD 1, PSA 115.27, QED 0.61
Compound (SMILES): CN(Cc1cccc(-c2cnc(N3CCN(c4ccc(C(=O)O)cc4Cl)CC3)nc2)c1)C(=O)CN
InChIKey: WUPBTBRKQPXTEW-UHFFFAOYSA-N
Target: Amine oxidase [copper-containing] 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08590
Assay: Inhibition Assay: A rat VAP-enzyme 1 (SSAO) activity was measured by a radiochemistry-enzymatic assay using 14C-benzylamine as an artificial substrate. An enzyme suspension prepared from CHO (Chinese Hamster Ovary) cells stably expressing a rat VAP-enzyme 1 (SSAO) was preincubated with the compound of the present invention in a 96-well microplate at room temperature for 30 minutes. Subsequently, the enzyme suspension was incubated with 14C-benzylamine (a final concentration of 1×10−5 mol/L) to a final volume of 50 mL at 37° C. for 1 hour. The enzymatic reaction was stopped by the addition of 2 mol/L (50 μL) of citric acid. The oxidation products were extracted directly in a 200-μL toluene scintillator, and the radioactivity was measured with a scintillation spectrometer.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 494.98, ALogP 2.74, HBA 7, HBD 2, PSA 115.89, QED 0.51
Compound (SMILES): C[C@@H](Oc1nc(Nc2ccc(S(=O)(=O)C3CC3)cc2)ncc1C(F)(F)F)C(C)(C)O
InChIKey: CFCFOHDIBWRIJY-LLVKDONJSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 445.46, ALogP 3.71, HBA 7, HBD 2, PSA 101.41, QED 0.67
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(=O)(=O)c3ccccc3)cc2)ncc1C(F)(F)F
InChIKey: CSDWDUQSLKTTMK-ZIAGYGMSSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 467.47, ALogP 4.22, HBA 7, HBD 2, PSA 101.41, QED 0.54
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(=O)(=O)C(F)F)cc2)ncc1C(F)(F)F
InChIKey: CDKIUTDNGTUHKC-RKDXNWHRSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 441.38, ALogP 3.38, HBA 7, HBD 2, PSA 101.41, QED 0.64
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(=O)(=O)C3CCCC3)cc2)ncc1C(F)(F)F
InChIKey: UVKIWKFJDSCWJY-CHWSQXEVSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 459.49, ALogP 4.1, HBA 7, HBD 2, PSA 101.41, QED 0.64
Compound (SMILES): C=CCS(=O)(=O)c1ccc(Nc2ncc(C(F)(F)F)c(O[C@H](C)C(C)(C)O)n2)cc1
InChIKey: JCPZVGATKUQPOE-GFCCVEGCSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 445.46, ALogP 3.74, HBA 7, HBD 2, PSA 101.41, QED 0.6
Compound (SMILES): CC(C)S(=O)(=O)c1ccc(Nc2ncc(C(F)(F)F)c(O[C@H](C)[C@@H](C)O)n2)cc1
InChIKey: KDLIWXJGIZBHKK-VXGBXAGGSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 433.45, ALogP 3.57, HBA 7, HBD 2, PSA 101.41, QED 0.69
Compound (SMILES): C#CCS(=O)(=O)c1ccc(Nc2ncc(C(F)(F)F)c(O[C@H](C)C(C)(C)O)n2)cc1
InChIKey: SDGMMQJEGBDKJW-GFCCVEGCSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 443.45, ALogP 3.18, HBA 7, HBD 2, PSA 101.41, QED 0.63
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(=O)(=O)CCO)cc2)ncc1C(F)(F)F
InChIKey: OKVAXHZNBTZJCB-GHMZBOCLSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 435.42, ALogP 2.15, HBA 8, HBD 3, PSA 121.64, QED 0.58
Compound (SMILES): COC[C@@H](C)Oc1nc(Nc2ccc(S(C)(=O)=O)cc2)ncc1C(F)(F)F
InChIKey: JFDFHRDTOSTHPU-SNVBAGLBSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 405.4, ALogP 3.06, HBA 7, HBD 1, PSA 90.41, QED 0.76
Compound (SMILES): C#CCOc1nc(Nc2ccc(S(C)(=O)=O)cc2)ncc1C(F)(F)F
InChIKey: PAICWQZQWHFNIR-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 371.34, ALogP 2.65, HBA 6, HBD 1, PSA 81.18, QED 0.81
Compound (SMILES): CS(=O)(=O)c1ccc(Nc2ncc(C(F)(F)F)c(OCCC(F)(F)F)n2)cc1
InChIKey: LOXABGFYQLXZMY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 429.34, ALogP 3.97, HBA 6, HBD 1, PSA 81.18, QED 0.7
Compound (SMILES): C=CCOc1nc(Nc2ccc(S(C)(=O)=O)cc2)ncc1C(F)(F)F
InChIKey: IUYBREVMXPBARL-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 373.36, ALogP 3.21, HBA 6, HBD 1, PSA 81.18, QED 0.78
Compound (SMILES): CS(=O)(=O)c1ccc(Nc2ncc(C(F)(F)F)c(OC3CCCCC3)n2)cc1
InChIKey: LMOGABSWSZHKQR-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 415.44, ALogP 4.35, HBA 6, HBD 1, PSA 81.18, QED 0.78
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(=O)(=O)C3CC3)cc2)ncc1C(F)(F)F
InChIKey: BAOWDLOLYGOWOE-GHMZBOCLSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 431.44, ALogP 3.32, HBA 7, HBD 2, PSA 101.41, QED 0.69
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(C)(=O)=O)cc2)ncc1C(F)(F)F
InChIKey: JLMIHNJHBAEFKC-NXEZZACHSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 405.4, ALogP 2.79, HBA 7, HBD 2, PSA 101.41, QED 0.76
Compound (SMILES): C[C@@H](Oc1nc(Nc2ccc(S(C)(=O)=O)cc2)ncc1C(F)(F)F)C(C)(C)O
InChIKey: PAEDTQQTYBULPN-SNVBAGLBSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Kinase Assay: CDK2/CycE (50 mg/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 uM) in assay buffer [50 mM Tris/HCl pH 8.0; 10 mM MgCl2; 0.1 mM Na ortho-vanadate; 1.0 mM dithiothreitol; 0.5 uM adenosine trisphosphate (ATP); 10 ug/measuring point histone IIIS; 0.2 uCi/measuring point 33P-gamma ATP; 0.05% NP40; 1.25% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C. The amount of incorporated 33P (substrate phosphorylation) was determined.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 419.43, ALogP 3.18, HBA 7, HBD 2, PSA 101.41, QED 0.74
Compound (SMILES): CC(C)(O)c1ccc(C(=O)Nc2cc3c(ccn3CC3CC3)cn2)cc1
InChIKey: OFLQFDPYHCROCP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Homogeneous Time-Resolved Fluorescence Assay: The inhibitory properties of compounds to ASK1 may be determined using a white 384-well-plate format under the following reaction conditions: 25 nM ASK1, 1 uM CisBio STK S3-biotion peptide, 100 uM ATP, and 1%-2% DMSO in kinase assay buffer of 50 mM HEPES, pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 0.2 mM EDTA, and 1 mM DTT. Reaction product is determined quantitatively by HTRF after the addition of detection reagent SA-XL665 and STK-antibody-cryptate.The assay reaction may be initiated as follows: 2 ul of the mixture of 3 uM CisBio STK S3-biotion peptide and 300 uM ATP with 2 ul of test compound (2 fold serial dilutions for 11 data points for each inhibitor) containing 3%-6% DMSO are added to each well of the plate, followed by the addition of 2 uL of 75 nM ASK1 to initiate the reaction (final enzyme concentration was 25 nM for ASK1). The reaction mixture may then be incubated at room temperature for 1 hour, and quenched and developed.
Measurement: IC50 = 237 nM (pChEMBL 6.619999885559082)
Descriptors: MW 349.43, ALogP 3.93, HBA 4, HBD 2, PSA 67.15, QED 0.73
Compound (SMILES): CC(C)(O)c1ccc(C(=O)Nc2cc3c(cn2)c(Br)cn3CC2CC2)cc1
InChIKey: MIIQFKVDBRZCLR-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Homogeneous Time-Resolved Fluorescence Assay: The inhibitory properties of compounds to ASK1 may be determined using a white 384-well-plate format under the following reaction conditions: 25 nM ASK1, 1 uM CisBio STK S3-biotion peptide, 100 uM ATP, and 1%-2% DMSO in kinase assay buffer of 50 mM HEPES, pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 0.2 mM EDTA, and 1 mM DTT. Reaction product is determined quantitatively by HTRF after the addition of detection reagent SA-XL665 and STK-antibody-cryptate.The assay reaction may be initiated as follows: 2 ul of the mixture of 3 uM CisBio STK S3-biotion peptide and 300 uM ATP with 2 ul of test compound (2 fold serial dilutions for 11 data points for each inhibitor) containing 3%-6% DMSO are added to each well of the plate, followed by the addition of 2 uL of 75 nM ASK1 to initiate the reaction (final enzyme concentration was 25 nM for ASK1). The reaction mixture may then be incubated at room temperature for 1 hour, and quenched and developed.
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 428.33, ALogP 4.69, HBA 4, HBD 2, PSA 67.15, QED 0.62
Compound (SMILES): CCn1cc(Br)c2cnc(NC(=O)c3ccc(C(C)(C)O)cc3)cc21
InChIKey: CXBAGEKVBRLQPB-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Homogeneous Time-Resolved Fluorescence Assay: The inhibitory properties of compounds to ASK1 may be determined using a white 384-well-plate format under the following reaction conditions: 25 nM ASK1, 1 uM CisBio STK S3-biotion peptide, 100 uM ATP, and 1%-2% DMSO in kinase assay buffer of 50 mM HEPES, pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 0.2 mM EDTA, and 1 mM DTT. Reaction product is determined quantitatively by HTRF after the addition of detection reagent SA-XL665 and STK-antibody-cryptate.The assay reaction may be initiated as follows: 2 ul of the mixture of 3 uM CisBio STK S3-biotion peptide and 300 uM ATP with 2 ul of test compound (2 fold serial dilutions for 11 data points for each inhibitor) containing 3%-6% DMSO are added to each well of the plate, followed by the addition of 2 uL of 75 nM ASK1 to initiate the reaction (final enzyme concentration was 25 nM for ASK1). The reaction mixture may then be incubated at room temperature for 1 hour, and quenched and developed.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 402.29, ALogP 4.3, HBA 4, HBD 2, PSA 67.15, QED 0.68
Compound (SMILES): CCn1cc(C)c2cnc(NC(=O)c3ccc(C(C)(C)O)cc3)cc21
InChIKey: ZQHKLPCNVZUFQJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Homogeneous Time-Resolved Fluorescence Assay: The inhibitory properties of compounds to ASK1 may be determined using a white 384-well-plate format under the following reaction conditions: 25 nM ASK1, 1 uM CisBio STK S3-biotion peptide, 100 uM ATP, and 1%-2% DMSO in kinase assay buffer of 50 mM HEPES, pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 0.2 mM EDTA, and 1 mM DTT. Reaction product is determined quantitatively by HTRF after the addition of detection reagent SA-XL665 and STK-antibody-cryptate.The assay reaction may be initiated as follows: 2 ul of the mixture of 3 uM CisBio STK S3-biotion peptide and 300 uM ATP with 2 ul of test compound (2 fold serial dilutions for 11 data points for each inhibitor) containing 3%-6% DMSO are added to each well of the plate, followed by the addition of 2 uL of 75 nM ASK1 to initiate the reaction (final enzyme concentration was 25 nM for ASK1). The reaction mixture may then be incubated at room temperature for 1 hour, and quenched and developed.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 337.42, ALogP 3.84, HBA 4, HBD 2, PSA 67.15, QED 0.76
Compound (SMILES): Cn1cc(Br)c2cnc(NC(=O)c3ccc(C(C)(C)O)cc3)cc21
InChIKey: XCXRNCCAOHYUGD-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Homogeneous Time-Resolved Fluorescence Assay: The inhibitory properties of compounds to ASK1 may be determined using a white 384-well-plate format under the following reaction conditions: 25 nM ASK1, 1 uM CisBio STK S3-biotion peptide, 100 uM ATP, and 1%-2% DMSO in kinase assay buffer of 50 mM HEPES, pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 0.2 mM EDTA, and 1 mM DTT. Reaction product is determined quantitatively by HTRF after the addition of detection reagent SA-XL665 and STK-antibody-cryptate.The assay reaction may be initiated as follows: 2 ul of the mixture of 3 uM CisBio STK S3-biotion peptide and 300 uM ATP with 2 ul of test compound (2 fold serial dilutions for 11 data points for each inhibitor) containing 3%-6% DMSO are added to each well of the plate, followed by the addition of 2 uL of 75 nM ASK1 to initiate the reaction (final enzyme concentration was 25 nM for ASK1). The reaction mixture may then be incubated at room temperature for 1 hour, and quenched and developed.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 388.27, ALogP 3.82, HBA 4, HBD 2, PSA 67.15, QED 0.72
Compound (SMILES): C[C@](O)(CO)c1ccc(C(=O)Nc2cc3c(ccn3C3CC3)cn2)cc1
InChIKey: KTWLWSBHHAXVSH-FQEVSTJZSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Homogeneous Time-Resolved Fluorescence Assay: The inhibitory properties of compounds to ASK1 may be determined using a white 384-well-plate format under the following reaction conditions: 25 nM ASK1, 1 uM CisBio STK S3-biotion peptide, 100 uM ATP, and 1%-2% DMSO in kinase assay buffer of 50 mM HEPES, pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 0.2 mM EDTA, and 1 mM DTT. Reaction product is determined quantitatively by HTRF after the addition of detection reagent SA-XL665 and STK-antibody-cryptate.The assay reaction may be initiated as follows: 2 ul of the mixture of 3 uM CisBio STK S3-biotion peptide and 300 uM ATP with 2 ul of test compound (2 fold serial dilutions for 11 data points for each inhibitor) containing 3%-6% DMSO are added to each well of the plate, followed by the addition of 2 uL of 75 nM ASK1 to initiate the reaction (final enzyme concentration was 25 nM for ASK1). The reaction mixture may then be incubated at room temperature for 1 hour, and quenched and developed.
Measurement: IC50 = 214 nM (pChEMBL 6.670000076293945)
Descriptors: MW 351.41, ALogP 2.82, HBA 5, HBD 3, PSA 87.38, QED 0.66
Compound (SMILES): Cc1cn(C)c2cc(NC(=O)c3ccc(C(C)(C)O)cc3)ncc12
InChIKey: CKKHADCGEGWKBX-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Homogeneous Time-Resolved Fluorescence Assay: The inhibitory properties of compounds to ASK1 may be determined using a white 384-well-plate format under the following reaction conditions: 25 nM ASK1, 1 uM CisBio STK S3-biotion peptide, 100 uM ATP, and 1%-2% DMSO in kinase assay buffer of 50 mM HEPES, pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 0.2 mM EDTA, and 1 mM DTT. Reaction product is determined quantitatively by HTRF after the addition of detection reagent SA-XL665 and STK-antibody-cryptate.The assay reaction may be initiated as follows: 2 ul of the mixture of 3 uM CisBio STK S3-biotion peptide and 300 uM ATP with 2 ul of test compound (2 fold serial dilutions for 11 data points for each inhibitor) containing 3%-6% DMSO are added to each well of the plate, followed by the addition of 2 uL of 75 nM ASK1 to initiate the reaction (final enzyme concentration was 25 nM for ASK1). The reaction mixture may then be incubated at room temperature for 1 hour, and quenched and developed.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 323.4, ALogP 3.36, HBA 4, HBD 2, PSA 67.15, QED 0.78
Compound (SMILES): C[C@](O)(CO)c1ccc(C(=O)Nc2cc3c(cn2)c(Br)cn3C2CC2)cc1
InChIKey: AGPTUNRVLHLJTR-FQEVSTJZSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Homogeneous Time-Resolved Fluorescence Assay: The inhibitory properties of compounds to ASK1 may be determined using a white 384-well-plate format under the following reaction conditions: 25 nM ASK1, 1 uM CisBio STK S3-biotion peptide, 100 uM ATP, and 1%-2% DMSO in kinase assay buffer of 50 mM HEPES, pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 0.2 mM EDTA, and 1 mM DTT. Reaction product is determined quantitatively by HTRF after the addition of detection reagent SA-XL665 and STK-antibody-cryptate.The assay reaction may be initiated as follows: 2 ul of the mixture of 3 uM CisBio STK S3-biotion peptide and 300 uM ATP with 2 ul of test compound (2 fold serial dilutions for 11 data points for each inhibitor) containing 3%-6% DMSO are added to each well of the plate, followed by the addition of 2 uL of 75 nM ASK1 to initiate the reaction (final enzyme concentration was 25 nM for ASK1). The reaction mixture may then be incubated at room temperature for 1 hour, and quenched and developed.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 430.3, ALogP 3.59, HBA 5, HBD 3, PSA 87.38, QED 0.58
Compound (SMILES): C[C@](O)(CO)c1ccc(C(=O)Nc2cc3c(cn2)c(Cl)cn3C2CC2)cc1
InChIKey: OJYSZUABAXPGIE-FQEVSTJZSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Homogeneous Time-Resolved Fluorescence Assay: The inhibitory properties of compounds to ASK1 may be determined using a white 384-well-plate format under the following reaction conditions: 25 nM ASK1, 1 uM CisBio STK S3-biotion peptide, 100 uM ATP, and 1%-2% DMSO in kinase assay buffer of 50 mM HEPES, pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 0.2 mM EDTA, and 1 mM DTT. Reaction product is determined quantitatively by HTRF after the addition of detection reagent SA-XL665 and STK-antibody-cryptate.The assay reaction may be initiated as follows: 2 ul of the mixture of 3 uM CisBio STK S3-biotion peptide and 300 uM ATP with 2 ul of test compound (2 fold serial dilutions for 11 data points for each inhibitor) containing 3%-6% DMSO are added to each well of the plate, followed by the addition of 2 uL of 75 nM ASK1 to initiate the reaction (final enzyme concentration was 25 nM for ASK1). The reaction mixture may then be incubated at room temperature for 1 hour, and quenched and developed.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 385.85, ALogP 3.48, HBA 5, HBD 3, PSA 87.38, QED 0.63
Compound (SMILES): Cn1cc(Cl)c2cnc(NC(=O)c3ccc(C(C)(C)O)cc3)cc21
InChIKey: HZDQWXQRWFHBHB-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Homogeneous Time-Resolved Fluorescence Assay: The inhibitory properties of compounds to ASK1 may be determined using a white 384-well-plate format under the following reaction conditions: 25 nM ASK1, 1 uM CisBio STK S3-biotion peptide, 100 uM ATP, and 1%-2% DMSO in kinase assay buffer of 50 mM HEPES, pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 0.2 mM EDTA, and 1 mM DTT. Reaction product is determined quantitatively by HTRF after the addition of detection reagent SA-XL665 and STK-antibody-cryptate.The assay reaction may be initiated as follows: 2 ul of the mixture of 3 uM CisBio STK S3-biotion peptide and 300 uM ATP with 2 ul of test compound (2 fold serial dilutions for 11 data points for each inhibitor) containing 3%-6% DMSO are added to each well of the plate, followed by the addition of 2 uL of 75 nM ASK1 to initiate the reaction (final enzyme concentration was 25 nM for ASK1). The reaction mixture may then be incubated at room temperature for 1 hour, and quenched and developed.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 343.81, ALogP 3.71, HBA 4, HBD 2, PSA 67.15, QED 0.76
Compound (SMILES): Cn1c(Cl)c(Cl)c2cnc(NC(=O)c3ccc(C(C)(C)O)cc3)cc21
InChIKey: JYCUSHKOWZOHEL-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Homogeneous Time-Resolved Fluorescence Assay: The inhibitory properties of compounds to ASK1 may be determined using a white 384-well-plate format under the following reaction conditions: 25 nM ASK1, 1 uM CisBio STK S3-biotion peptide, 100 uM ATP, and 1%-2% DMSO in kinase assay buffer of 50 mM HEPES, pH 7.3, 10 mM NaCl, 10 mM MgCl2, 0.01% Brij35, 0.2 mM EDTA, and 1 mM DTT. Reaction product is determined quantitatively by HTRF after the addition of detection reagent SA-XL665 and STK-antibody-cryptate.The assay reaction may be initiated as follows: 2 ul of the mixture of 3 uM CisBio STK S3-biotion peptide and 300 uM ATP with 2 ul of test compound (2 fold serial dilutions for 11 data points for each inhibitor) containing 3%-6% DMSO are added to each well of the plate, followed by the addition of 2 uL of 75 nM ASK1 to initiate the reaction (final enzyme concentration was 25 nM for ASK1). The reaction mixture may then be incubated at room temperature for 1 hour, and quenched and developed.
Measurement: IC50 = 146 nM (pChEMBL 6.840000152587891)
Descriptors: MW 378.26, ALogP 4.36, HBA 4, HBD 2, PSA 67.15, QED 0.71
Compound (SMILES): Cc1cccc(Cn2nc(C3CC3)c3c(NC(=O)c4cnc5cc(OCCN6CCN(C)CC6)ccn45)cccc32)n1
InChIKey: JUPOTOIJLKDAPF-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: LANCE Ultra TR-FRET Assay: The ability of compounds of Formula I to inhibit cFMS was determined by the following assay. cFMS enzymatic activity was measured using the LANCE Ultra TR-FRET assay technology from PerkinElmer (Waltham, Mass.). Incubation mixtures contained the following: 50 mM NaHEPES, pH 7.3, 10 mM MgCl2, 0.5 mM MnCl2, 0.01% Triton X-100, 1 mM DTT, 1% DMSO, 10 uM ATP, 25 nM LANCE Ultra ULight-poly GAT and 0.5 nM cFMS in a total volume of 10 uL. The concentration of compounds of Formula I was varied over 10-point, 3-fold dilution series with 10,000 nM typically being the highest dose. Incubations were carried out in white ProxyPlate-384 Plus plates (PerkinElmer) at 22 C. for 20 minutes, after which 10 uL of a quench/detection solution was added containing 1x LANCE Detection Buffer, 2 nM LANCE EuW1024 Anti-phosphotyrosine (PY20) and 36 mM EDTA. After an additional 60 minutes incubation at 22 C., the assay plate was read on an EnVision 2103 Multilabel Reader (PerkinElmer).
Measurement: IC50 = 93.6 nM (pChEMBL 7.03000020980835)
Descriptors: MW 564.69, ALogP 4.19, HBA 9, HBD 1, PSA 92.82, QED 0.29
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: MECRBBLUTQSQAP-ZLCORKTQSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 1067.23
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: DHQKURVDSAVGBS-IJRTVYNZSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 1058.26