lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(N2CCN(C3CCOCC3)CC2)ccc1Nc1ncc2c(n1)-c1c(nn(C)c1Cc1cccc(Cl)c1)CC2
InChIKey: KKDSJPYLRKITAS-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 600.17, ALogP 5.27, HBA 9, HBD 1, PSA 80.57, QED 0.31
Compound (SMILES): COc1cc(N2CCN(C3CCN(C(C)=O)CC3)CC2)ccc1Nc1ncc2c(n1)-c1c(nn(C)c1Cc1cccc(Cl)c1)CC2
InChIKey: JBRCSLRQHLPZBV-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 641.22, ALogP 5.11, HBA 9, HBD 1, PSA 91.65, QED 0.3
Compound (SMILES): COc1cc(N2CCN(C(C)C)CC2)ccc1Nc1ncc2c(n1)-c1c(nn(C)c1Cc1cccc(Cl)c1)CC2
InChIKey: ZPBFFDZENYVNHX-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 558.13, ALogP 5.5, HBA 8, HBD 1, PSA 71.34, QED 0.32
Compound (SMILES): CCN1CCN(c2ccc(Nc3ncc4c(n3)-c3c(nn(C)c3Cc3cccc(Cl)c3)CC4)c(OC)c2)CC1
InChIKey: DYBQWTPWJPAYIN-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 544.1, ALogP 5.11, HBA 8, HBD 1, PSA 71.34, QED 0.35
Compound (SMILES): CC1Cc2nn(C)c(Cc3ccccc3Cl)c2-c2nc(Nc3cnn(C4CCN(C5CCOCC5)CC4)c3)ncc21
InChIKey: QGZVOUDDTFYAME-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 573.15, ALogP 5.54, HBA 9, HBD 1, PSA 85.92, QED 0.32
Compound (SMILES): CC(=O)N1CCC(N2CCC(n3cc(Nc4ncc5c(n4)-c4c(nn(C)c4Cc4ccccc4Cl)CC5C)cn3)CC2)CC1
InChIKey: QFQNHTDMQSXDJH-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 614.2, ALogP 5.37, HBA 9, HBD 1, PSA 97, QED 0.31
Compound (SMILES): CC1Cc2nn(C)c(Cc3ccccc3Cl)c2-c2nc(Nc3cnn(C4CCN(CCO)CC4)c3)ncc21
InChIKey: RBKDEMAVXNDVAI-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 533.08, ALogP 4.35, HBA 9, HBD 2, PSA 96.92, QED 0.37
Compound (SMILES): CCOc1cc(N2CCN(S(C)(=O)=O)CC2)ccc1Nc1ncc2c(n1)-c1c(nn(C)c1Cc1ccccc1)CC2
InChIKey: JDSBSZUXTUNTSA-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 573.72, ALogP 3.79, HBA 9, HBD 1, PSA 105.48, QED 0.34
Compound (SMILES): CCOc1cc(N2CCN(C(=O)N(C)C)CC2)ccc1Nc1ncc2c(n1)-c1c(nn(C)c1Cc1ccccc1)CC2
InChIKey: CYCHDIHEXRZQMY-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 566.71, ALogP 4.51, HBA 8, HBD 1, PSA 91.65, QED 0.35
Compound (SMILES): Cc1ccccc1-c1c2c(nn1C)CCc1cnc(Nc3ccc(OCC(C)(C)CN(C)C)cc3Cl)nc1-2
InChIKey: XHDBJEZJXSMVRH-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 531.1, ALogP 6.31, HBA 7, HBD 1, PSA 68.1, QED 0.29
Compound (SMILES): Cc1ccccc1-c1c2c(nn1C)CCc1cnc(Nc3ccc(OCCCN(C)C)cc3Cl)nc1-2
InChIKey: NOOGZOLAKXALDZ-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 503.05, ALogP 5.68, HBA 7, HBD 1, PSA 68.1, QED 0.31
Compound (SMILES): Cc1ccccc1-c1c2c(nn1C)CCc1cnc(Nc3ccc(OC4CCN(C)CC4)cc3Cl)nc1-2
InChIKey: TYLMXZYUZRGYOA-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 515.06, ALogP 5.82, HBA 7, HBD 1, PSA 68.1, QED 0.36
Compound (SMILES): Cc1ccccc1-c1c2c(nn1C)CCc1cnc(Nc3ccc(OCCN(C)C)cc3Cl)nc1-2
InChIKey: GESRLJSNHTUMIF-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 489.02, ALogP 5.29, HBA 7, HBD 1, PSA 68.1, QED 0.38
Compound (SMILES): Cc1ccccc1-c1c2c(nn1C)CCc1cnc(Nc3ccc(OCC(C)(C)N(C)C)cc3Cl)nc1-2
InChIKey: PVPAUVKLFFSVQF-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 517.08, ALogP 6.07, HBA 7, HBD 1, PSA 68.1, QED 0.32
Compound (SMILES): Cc1ccccc1-c1c2c(nn1C)CCc1cnc(Nc3ccc(OCCCN4CCCC4)cc3Cl)nc1-2
InChIKey: SSWUHFXOXMQKPW-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 529.09, ALogP 6.21, HBA 7, HBD 1, PSA 68.1, QED 0.27
Compound (SMILES): CCCn1nc2c(c1C(C)C)-c1nc(Nc3ccc(OCCN4CCCC4)cc3OC)ncc1CC2
InChIKey: OMPLTNBYAYADEI-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 490.65, ALogP 5.2, HBA 8, HBD 1, PSA 77.33, QED 0.42
Compound (SMILES): COc1cc(OCCN2CCCC2)ccc1Nc1ncc2c(n1)-c1c(nn(C(C)C)c1C(C)C)CC2
InChIKey: KFFHHZUSGLUZPR-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: DELFIA assay: The kinase activity is measured by DELFIA assay (dissociation-enhanced lanthanide fluorescence immunoassay, Perkin Elmer). The cytoplasmic kinase domain of human IGF-1R (amino acids 964-1370) is expressed as a fusion protein with a glutathione-S-transferase tag (IGF-1R-GST) in High Five Cells (Invitrogen). Enzyme activity is measured in the presence of substances and a control substance. Poly-glutamate-tyrosine peptide (pEY, Sigma Aldrich) and biotinylated pEY (bio-pEY) are used as reaction substrates. 10 uL of substance in 25% DMSO are mixed with 30 uL of IGF-1R-GST solution (67 mM HEPES pH 7.4, 15 ug/mL pEY, 1.7 ug/mL bio-pEY, 13.3 mM MgCl2, 3.3 mM dithiothreitol, 0.0033% Brij 35, 2 ng IGF-1R-GST) in 96-well plates. The reactions are started with 10 uL of a 750 uM ATP solution. After 40 min at RT the reactions are stopped with 50 uL of stop solution (250 mM EDTA, 20 mM HEPES pH 7.4).
Measurement: IC50 = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 490.65, ALogP 5.37, HBA 8, HBD 1, PSA 77.33, QED 0.43
Compound (SMILES): C#C[C@@H]1CN(C(=O)[C@H](CC(C)C)NC(=O)c2ccc(-c3csc(N4CCN(C)CC4)n3)cc2)[C@@H]2C(=O)CO[C@H]12
InChIKey: FIJFMUKDMVGIOK-ZRYIBQHNSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Enzyme Assay: Standard assay conditions for the determination of kinetic constants used a fluorogenic peptide substrate, typically H-D-Ala-Leu-Lys-AMC, and were determined in either 100 mM Mes/Tris, pH 7.0 containing 1 mM EDTA and 10 mM 2-mercaptoethanol or 100 mM Na phosphate, imM EDTA, 0.1% PEG4000 pH 6.5 or 100 mM Na acetate, pH 5.5 containing 5 mM EDTA and 20 mM cysteine, in each case optionally with 1M DTT as stabiliser. The enzyme concentration used was 5 nM. The stock substrate solution was prepared at 10 mM in DMSO. Screens were carried out at a fixed substrate concentration of 60 μM and detailed kinetic studies with doubling dilutions of substrate from 250 μM. The total DMSO concentration in the assay was kept below 3%. All assays were conducted at ambient temperature. Product fluorescence (excitation at 390 nm, emission at 460 nm) was monitored with a Labsystems Fluoroskan Ascent fluorescent plate reader.
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 549.7, ALogP 2.13, HBA 8, HBD 1, PSA 95.08, QED 0.53
Compound (SMILES): C#C[C@@H]1CN(C(=O)[C@H](CC(C)C)NC(=O)c2ccc(-c3nc(N4CCN(C)CC4)sc3F)cc2)[C@@H]2C(=O)CO[C@H]12
InChIKey: HUMYXJUMFCJTGM-KWACHACRSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Enzyme Assay: Standard assay conditions for the determination of kinetic constants used a fluorogenic peptide substrate, typically H-D-Ala-Leu-Lys-AMC, and were determined in either 100 mM Mes/Tris, pH 7.0 containing 1 mM EDTA and 10 mM 2-mercaptoethanol or 100 mM Na phosphate, imM EDTA, 0.1% PEG4000 pH 6.5 or 100 mM Na acetate, pH 5.5 containing 5 mM EDTA and 20 mM cysteine, in each case optionally with 1M DTT as stabiliser. The enzyme concentration used was 5 nM. The stock substrate solution was prepared at 10 mM in DMSO. Screens were carried out at a fixed substrate concentration of 60 μM and detailed kinetic studies with doubling dilutions of substrate from 250 μM. The total DMSO concentration in the assay was kept below 3%. All assays were conducted at ambient temperature. Product fluorescence (excitation at 390 nm, emission at 460 nm) was monitored with a Labsystems Fluoroskan Ascent fluorescent plate reader.
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 567.69, ALogP 2.27, HBA 8, HBD 1, PSA 95.08, QED 0.51
Compound (SMILES): C#C[C@@H]1CN(C(=O)[C@H](CC(C)C)NC(=O)c2ccc(-c3csc(N4CCN(C)CC4)n3)c(F)c2)[C@@H]2C(=O)CO[C@H]12
InChIKey: RFCUHPQJTGIXFS-GTKJVGNCSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Enzyme Assay: Standard assay conditions for the determination of kinetic constants used a fluorogenic peptide substrate, typically H-D-Ala-Leu-Lys-AMC, and were determined in either 100 mM Mes/Tris, pH 7.0 containing 1 mM EDTA and 10 mM 2-mercaptoethanol or 100 mM Na phosphate, imM EDTA, 0.1% PEG4000 pH 6.5 or 100 mM Na acetate, pH 5.5 containing 5 mM EDTA and 20 mM cysteine, in each case optionally with 1M DTT as stabiliser. The enzyme concentration used was 5 nM. The stock substrate solution was prepared at 10 mM in DMSO. Screens were carried out at a fixed substrate concentration of 60 μM and detailed kinetic studies with doubling dilutions of substrate from 250 μM. The total DMSO concentration in the assay was kept below 3%. All assays were conducted at ambient temperature. Product fluorescence (excitation at 390 nm, emission at 460 nm) was monitored with a Labsystems Fluoroskan Ascent fluorescent plate reader.
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 567.69, ALogP 2.27, HBA 8, HBD 1, PSA 95.08, QED 0.51
Compound (SMILES): CC(C)=C[C@@H]1CN(C(=O)[C@H](CC(C)C)NC(=O)c2ccc(-c3nc(N4CCN(C)CC4)sc3F)cc2)[C@@H]2C(=O)CO[C@H]12
InChIKey: UTDIUZBVSSNGOU-QGNCETNGSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Enzyme Assay: Standard assay conditions for the determination of kinetic constants used a fluorogenic peptide substrate, typically H-D-Ala-Leu-Lys-AMC, and were determined in either 100 mM Mes/Tris, pH 7.0 containing 1 mM EDTA and 10 mM 2-mercaptoethanol or 100 mM Na phosphate, imM EDTA, 0.1% PEG4000 pH 6.5 or 100 mM Na acetate, pH 5.5 containing 5 mM EDTA and 20 mM cysteine, in each case optionally with 1M DTT as stabiliser. The enzyme concentration used was 5 nM. The stock substrate solution was prepared at 10 mM in DMSO. Screens were carried out at a fixed substrate concentration of 60 μM and detailed kinetic studies with doubling dilutions of substrate from 250 μM. The total DMSO concentration in the assay was kept below 3%. All assays were conducted at ambient temperature. Product fluorescence (excitation at 390 nm, emission at 460 nm) was monitored with a Labsystems Fluoroskan Ascent fluorescent plate reader.
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 597.76, ALogP 3.61, HBA 8, HBD 1, PSA 95.08, QED 0.46
Compound (SMILES): C#C[C@@H]1CN(C(=O)[C@@H](NC(=O)c2ccc(-c3nc(N4CCN(C)CC4)sc3F)cc2)C2CCCC2)[C@@H]2C(=O)CO[C@H]12
InChIKey: DEMUCOOCKQGXOE-SXEIHZRZSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Cathepsin S Ki Determination: The assay uses baculovirus-expressed human cathepsin S and the boc-Val-Leu-Lys-AMC fluorescent substrate available from Bachem in a 384 well plate format, in which 7 test compounds can be tested in parallel with a positive control comprising a known cathepsin S inhibitor comparator.
Measurement: Ki = 1170 nM (pChEMBL 5.929999828338623)
Descriptors: MW 579.7, ALogP 2.42, HBA 8, HBD 1, PSA 95.08, QED 0.53
Compound (SMILES): Fc1cnc2[nH]nc(Nc3cc(C(F)(F)F)cc(-c4ccccc4Cl)n3)c2c1
InChIKey: GBGNHUZQFPYZRM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition Assay: Compounds of the present invention were screened for their ability to inhibit GSK-3β (AA 1-420) activity using a standard coupled enzyme system (Fox et al., Protein Sci. 1998, 7, 2249). Reactions were carried out in a solution containing 100 mM HEPES (pH 7.5), 10 mM MgCl2, 25 mM NaCl, 300 μM NADH, 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 20 μM ATP (Sigma Chemicals, St Louis, Mo.) and 300 μM peptide (American Peptide, Sunnyvale, Calif.). Reactions were carried out at 30 C. and 20 nM GSK-3β. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 μM NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 407.76, ALogP 5.57, HBA 4, HBD 2, PSA 66.49, QED 0.44
Compound (SMILES): Cc1cc(Nc2n[nH]c3ncc(F)cc23)nc(-c2ccccc2Cl)c1C
InChIKey: MVUKVIIMDNACQW-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition Assay: Compounds of the present invention were screened for their ability to inhibit GSK-3β (AA 1-420) activity using a standard coupled enzyme system (Fox et al., Protein Sci. 1998, 7, 2249). Reactions were carried out in a solution containing 100 mM HEPES (pH 7.5), 10 mM MgCl2, 25 mM NaCl, 300 μM NADH, 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 20 μM ATP (Sigma Chemicals, St Louis, Mo.) and 300 μM peptide (American Peptide, Sunnyvale, Calif.). Reactions were carried out at 30 C. and 20 nM GSK-3β. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 μM NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 367.82, ALogP 5.17, HBA 4, HBD 2, PSA 66.49, QED 0.52
Compound (SMILES): Cc1cc(Nc2n[nH]c3ncc(F)cc23)nc(-c2ccccc2Cl)c1
InChIKey: QAFFAZAVQKPMKM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition Assay: Compounds of the present invention were screened for their ability to inhibit GSK-3β (AA 1-420) activity using a standard coupled enzyme system (Fox et al., Protein Sci. 1998, 7, 2249). Reactions were carried out in a solution containing 100 mM HEPES (pH 7.5), 10 mM MgCl2, 25 mM NaCl, 300 μM NADH, 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 20 μM ATP (Sigma Chemicals, St Louis, Mo.) and 300 μM peptide (American Peptide, Sunnyvale, Calif.). Reactions were carried out at 30 C. and 20 nM GSK-3β. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 μM NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 353.79, ALogP 4.86, HBA 4, HBD 2, PSA 66.49, QED 0.55
Compound (SMILES): Cc1cc(-c2ccccc2Cl)nc(Nc2n[nH]c3ncc(F)cc23)c1C
InChIKey: ZHZPUYSNZQKXRF-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition Assay: Compounds of the present invention were screened for their ability to inhibit GSK-3β (AA 1-420) activity using a standard coupled enzyme system (Fox et al., Protein Sci. 1998, 7, 2249). Reactions were carried out in a solution containing 100 mM HEPES (pH 7.5), 10 mM MgCl2, 25 mM NaCl, 300 μM NADH, 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 20 μM ATP (Sigma Chemicals, St Louis, Mo.) and 300 μM peptide (American Peptide, Sunnyvale, Calif.). Reactions were carried out at 30 C. and 20 nM GSK-3β. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 μM NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 367.82, ALogP 5.17, HBA 4, HBD 2, PSA 66.49, QED 0.52
Compound (SMILES): Cc1cc(Nc2n[nH]c3ncc(F)cc23)nc(-c2ccccc2)c1C
InChIKey: RAUNAZYXRMQIJT-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition Assay: Compounds of the present invention were screened for their ability to inhibit GSK-3β (AA 1-420) activity using a standard coupled enzyme system (Fox et al., Protein Sci. 1998, 7, 2249). Reactions were carried out in a solution containing 100 mM HEPES (pH 7.5), 10 mM MgCl2, 25 mM NaCl, 300 μM NADH, 1 mM DTT and 1.5% DMSO. Final substrate concentrations in the assay were 20 μM ATP (Sigma Chemicals, St Louis, Mo.) and 300 μM peptide (American Peptide, Sunnyvale, Calif.). Reactions were carried out at 30 C. and 20 nM GSK-3β. Final concentrations of the components of the coupled enzyme system were 2.5 mM phosphoenolpyruvate, 300 μM NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 333.37, ALogP 4.52, HBA 4, HBD 2, PSA 66.49, QED 0.58
Compound (SMILES): O=c1[nH]c(CC2CCCCC2)nc2c1cnn2C1CCCC1
InChIKey: VWQYGWICBIKZQO-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: In Vitro Inhibition Assay: The test substances are dissolved in 100% DMSO and serially diluted to determine their in vitro effect on PDE 9A. 2 uL portions of the diluted substance solutions are introduced into the wells of microtiter plates (Isoplate; Wallac Inc., Atlanta, Ga.). Then 50 uL of a dilution of the PDE9A preparation described above are added. The dilution of the PDE9A preparation is chosen so that less than 70% of the substrate is converted during the subsequent incubation (typical dilution: 1:10000; dilution buffer: 50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA, 0.2% BSA). The substrate, [8-3H] guanosine 3',5'-cyclic phosphate (1 uCi/uL; Amersham Pharmacia Biotech., Piscataway, N.J.) is diluted 1:2000 with assay buffer (50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA) to a concentration of 0.0005 uCi/uL.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 300.41, ALogP 3.36, HBA 4, HBD 1, PSA 63.57, QED 0.95
Compound (SMILES): CCC(CC)n1ncc2c(=O)[nH]c(CC3CCCCC3)nc21
InChIKey: GXWSVMJGLJNVHK-UHFFFAOYSA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q14123
Assay: In Vitro Inhibition Assay: The test substances are dissolved in 100% DMSO and serially diluted to determine their in vitro effect on PDE 9A. 2 uL portions of the diluted substance solutions are introduced into the wells of microtiter plates (Isoplate; Wallac Inc., Atlanta, Ga.). Then 50 uL of a dilution of the PDE9A preparation described above are added. The dilution of the PDE9A preparation is chosen so that less than 70% of the substrate is converted during the subsequent incubation (typical dilution: 1:10000; dilution buffer: 50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA, 0.2% BSA). The substrate, [8-3H] guanosine 3',5'-cyclic phosphate (1 uCi/uL; Amersham Pharmacia Biotech., Piscataway, N.J.) is diluted 1:2000 with assay buffer (50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA) to a concentration of 0.0005 uCi/uL.
Measurement: IC50 = 720 nM (pChEMBL 6.139999866485596)
Descriptors: MW 302.42, ALogP 3.6, HBA 4, HBD 1, PSA 63.57, QED 0.92
Compound (SMILES): CCC(C)Cc1nc2c(cnn2C2CCCC2)c(=O)[nH]1
InChIKey: CMRWPJDNENEYTL-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: In Vitro Inhibition Assay: The test substances are dissolved in 100% DMSO and serially diluted to determine their in vitro effect on PDE 9A. 2 uL portions of the diluted substance solutions are introduced into the wells of microtiter plates (Isoplate; Wallac Inc., Atlanta, Ga.). Then 50 uL of a dilution of the PDE9A preparation described above are added. The dilution of the PDE9A preparation is chosen so that less than 70% of the substrate is converted during the subsequent incubation (typical dilution: 1:10000; dilution buffer: 50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA, 0.2% BSA). The substrate, [8-3H] guanosine 3',5'-cyclic phosphate (1 uCi/uL; Amersham Pharmacia Biotech., Piscataway, N.J.) is diluted 1:2000 with assay buffer (50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA) to a concentration of 0.0005 uCi/uL.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 274.37, ALogP 2.82, HBA 4, HBD 1, PSA 63.57, QED 0.93
Compound (SMILES): O=c1[nH]c(CC2C=CCC2)nc2c1cnn2C1CCCC1
InChIKey: KIDQOAJBNXNQBE-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: In Vitro Inhibition Assay: The test substances are dissolved in 100% DMSO and serially diluted to determine their in vitro effect on PDE 9A. 2 uL portions of the diluted substance solutions are introduced into the wells of microtiter plates (Isoplate; Wallac Inc., Atlanta, Ga.). Then 50 uL of a dilution of the PDE9A preparation described above are added. The dilution of the PDE9A preparation is chosen so that less than 70% of the substrate is converted during the subsequent incubation (typical dilution: 1:10000; dilution buffer: 50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA, 0.2% BSA). The substrate, [8-3H] guanosine 3',5'-cyclic phosphate (1 uCi/uL; Amersham Pharmacia Biotech., Piscataway, N.J.) is diluted 1:2000 with assay buffer (50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA) to a concentration of 0.0005 uCi/uL.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 284.36, ALogP 2.74, HBA 4, HBD 1, PSA 63.57, QED 0.88
Compound (SMILES): CCC(CC)n1ncc2c(=O)[nH]c(CC3C=CCC3)nc21
InChIKey: KJPOHYCINXMVCC-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: In Vitro Inhibition Assay: The test substances are dissolved in 100% DMSO and serially diluted to determine their in vitro effect on PDE 9A. 2 uL portions of the diluted substance solutions are introduced into the wells of microtiter plates (Isoplate; Wallac Inc., Atlanta, Ga.). Then 50 uL of a dilution of the PDE9A preparation described above are added. The dilution of the PDE9A preparation is chosen so that less than 70% of the substrate is converted during the subsequent incubation (typical dilution: 1:10000; dilution buffer: 50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA, 0.2% BSA). The substrate, [8-3H] guanosine 3',5'-cyclic phosphate (1 uCi/uL; Amersham Pharmacia Biotech., Piscataway, N.J.) is diluted 1:2000 with assay buffer (50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA) to a concentration of 0.0005 uCi/uL.
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 286.38, ALogP 2.99, HBA 4, HBD 1, PSA 63.57, QED 0.86
Compound (SMILES): O=c1[nH]c(CC2CCCO2)nc2c1cnn2C1CCCC1
InChIKey: XRSRRHPUNLFRMH-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: In Vitro Inhibition Assay: The test substances are dissolved in 100% DMSO and serially diluted to determine their in vitro effect on PDE 9A. 2 uL portions of the diluted substance solutions are introduced into the wells of microtiter plates (Isoplate; Wallac Inc., Atlanta, Ga.). Then 50 uL of a dilution of the PDE9A preparation described above are added. The dilution of the PDE9A preparation is chosen so that less than 70% of the substrate is converted during the subsequent incubation (typical dilution: 1:10000; dilution buffer: 50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA, 0.2% BSA). The substrate, [8-3H] guanosine 3',5'-cyclic phosphate (1 uCi/uL; Amersham Pharmacia Biotech., Piscataway, N.J.) is diluted 1:2000 with assay buffer (50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA) to a concentration of 0.0005 uCi/uL.
Measurement: IC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 288.35, ALogP 1.96, HBA 5, HBD 1, PSA 72.8, QED 0.94
Compound (SMILES): CCC(CC)n1ncc2c(=S)[nH]c(CC3CCCCC3)nc21
InChIKey: PHBFLKWXWNOHHC-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: In Vitro Inhibition Assay: The test substances are dissolved in 100% DMSO and serially diluted to determine their in vitro effect on PDE 9A. 2 uL portions of the diluted substance solutions are introduced into the wells of microtiter plates (Isoplate; Wallac Inc., Atlanta, Ga.). Then 50 uL of a dilution of the PDE9A preparation described above are added. The dilution of the PDE9A preparation is chosen so that less than 70% of the substrate is converted during the subsequent incubation (typical dilution: 1:10000; dilution buffer: 50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA, 0.2% BSA). The substrate, [8-3H] guanosine 3',5'-cyclic phosphate (1 uCi/uL; Amersham Pharmacia Biotech., Piscataway, N.J.) is diluted 1:2000 with assay buffer (50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA) to a concentration of 0.0005 uCi/uL.
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 318.49, ALogP 4.97, HBA 4, HBD 1, PSA 46.5, QED 0.79
Compound (SMILES): CCOc1cc(C2NC(=O)N=C(c3ccccc3)C2c2ccccc2)cc([N+](=O)[O-])c1O
InChIKey: QOVFYKJDUHRDDL-UHFFFAOYSA-N
Target: Alcohol dehydrogenase class-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11766
Assay: GSNOR Assay: GSNO and Enzyme/NADH Solutions are made up fresh each day. The Solutions are filtered and allowed to warm to room temperature. GSNO Solution: 100 mM NaPO4 (pH 7.4), 0.480 mM GSNO. 396 μL of GSNO Solution is added to a cuvette followed by 8 μL of test compound in DMSO (or DMSO only for full reaction control) and mixed with the pipette tip. Compounds to be tested are made up at a stock concentration of 10 mM in 100% DMSO. 2 fold serial dilutions are done in 100% DMSO. 8 μL of each dilution are added to an assay so that the final concentration of DMSO in the assay is 1%. The concentrations of compounds tested range from 100 to 0.003 μM. Enzyme/NADH Solution: 100 mM NaPO4 (pH 7.4), 0.600 mM NADH, 1.0 μg/mL GSNO Reductase. 396 μL of the Enzyme/NADH Solution is added to the cuvette to start the reaction.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 431.45, ALogP 4.74, HBA 5, HBD 2, PSA 114.06, QED 0.43
Compound (SMILES): CCOc1cc(C2NC(=O)N=C(c3ccccc3)C2c2ccsc2)cc([N+](=O)[O-])c1O
InChIKey: AKDQCRSWAYXLAK-UHFFFAOYSA-N
Target: Alcohol dehydrogenase class-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11766
Assay: GSNOR Assay: GSNO and Enzyme/NADH Solutions are made up fresh each day. The Solutions are filtered and allowed to warm to room temperature. GSNO Solution: 100 mM NaPO4 (pH 7.4), 0.480 mM GSNO. 396 μL of GSNO Solution is added to a cuvette followed by 8 μL of test compound in DMSO (or DMSO only for full reaction control) and mixed with the pipette tip. Compounds to be tested are made up at a stock concentration of 10 mM in 100% DMSO. 2 fold serial dilutions are done in 100% DMSO. 8 μL of each dilution are added to an assay so that the final concentration of DMSO in the assay is 1%. The concentrations of compounds tested range from 100 to 0.003 μM. Enzyme/NADH Solution: 100 mM NaPO4 (pH 7.4), 0.600 mM NADH, 1.0 μg/mL GSNO Reductase. 396 μL of the Enzyme/NADH Solution is added to the cuvette to start the reaction.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 437.48, ALogP 4.8, HBA 6, HBD 2, PSA 114.06, QED 0.42
Compound (SMILES): CCOc1cc(C2NC(=O)N=C(c3cccnc3)C2c2ccccc2)cc([N+](=O)[O-])c1O
InChIKey: ADNUWBLFRFEGIQ-UHFFFAOYSA-N
Target: Alcohol dehydrogenase class-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11766
Assay: GSNOR Assay: GSNO and Enzyme/NADH Solutions are made up fresh each day. The Solutions are filtered and allowed to warm to room temperature. GSNO Solution: 100 mM NaPO4 (pH 7.4), 0.480 mM GSNO. 396 μL of GSNO Solution is added to a cuvette followed by 8 μL of test compound in DMSO (or DMSO only for full reaction control) and mixed with the pipette tip. Compounds to be tested are made up at a stock concentration of 10 mM in 100% DMSO. 2 fold serial dilutions are done in 100% DMSO. 8 μL of each dilution are added to an assay so that the final concentration of DMSO in the assay is 1%. The concentrations of compounds tested range from 100 to 0.003 μM. Enzyme/NADH Solution: 100 mM NaPO4 (pH 7.4), 0.600 mM NADH, 1.0 μg/mL GSNO Reductase. 396 μL of the Enzyme/NADH Solution is added to the cuvette to start the reaction.
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 432.44, ALogP 4.13, HBA 6, HBD 2, PSA 126.95, QED 0.45
Compound (SMILES): CCOc1cc(C2NC(=O)N=C(c3cccnc3)C2c2ccsc2)cc([N+](=O)[O-])c1O
InChIKey: JHVSIYWXTWMWDN-UHFFFAOYSA-N
Target: Alcohol dehydrogenase class-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11766
Assay: GSNOR Assay: GSNO and Enzyme/NADH Solutions are made up fresh each day. The Solutions are filtered and allowed to warm to room temperature. GSNO Solution: 100 mM NaPO4 (pH 7.4), 0.480 mM GSNO. 396 μL of GSNO Solution is added to a cuvette followed by 8 μL of test compound in DMSO (or DMSO only for full reaction control) and mixed with the pipette tip. Compounds to be tested are made up at a stock concentration of 10 mM in 100% DMSO. 2 fold serial dilutions are done in 100% DMSO. 8 μL of each dilution are added to an assay so that the final concentration of DMSO in the assay is 1%. The concentrations of compounds tested range from 100 to 0.003 μM. Enzyme/NADH Solution: 100 mM NaPO4 (pH 7.4), 0.600 mM NADH, 1.0 μg/mL GSNO Reductase. 396 μL of the Enzyme/NADH Solution is added to the cuvette to start the reaction.
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 438.47, ALogP 4.19, HBA 7, HBD 2, PSA 126.95, QED 0.44
Compound (SMILES): CCOc1cc(C2NC(=O)N=C(c3ccn(C)n3)C2c2ccsc2)cc([N+](=O)[O-])c1O
InChIKey: HSSNRDLONYUNIO-UHFFFAOYSA-N
Target: Alcohol dehydrogenase class-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11766
Assay: GSNOR Assay: GSNO and Enzyme/NADH Solutions are made up fresh each day. The Solutions are filtered and allowed to warm to room temperature. GSNO Solution: 100 mM NaPO4 (pH 7.4), 0.480 mM GSNO. 396 μL of GSNO Solution is added to a cuvette followed by 8 μL of test compound in DMSO (or DMSO only for full reaction control) and mixed with the pipette tip. Compounds to be tested are made up at a stock concentration of 10 mM in 100% DMSO. 2 fold serial dilutions are done in 100% DMSO. 8 μL of each dilution are added to an assay so that the final concentration of DMSO in the assay is 1%. The concentrations of compounds tested range from 100 to 0.003 μM. Enzyme/NADH Solution: 100 mM NaPO4 (pH 7.4), 0.600 mM NADH, 1.0 μg/mL GSNO Reductase. 396 μL of the Enzyme/NADH Solution is added to the cuvette to start the reaction.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 441.47, ALogP 3.53, HBA 8, HBD 2, PSA 131.88, QED 0.44
Compound (SMILES): CCOc1cc([C@H]2NC(=O)N=C(c3cccnc3)C2c2ccsc2)cc(C(=O)O)c1O
InChIKey: LBQQJPUROPEYKE-WHCXFUJUSA-N
Target: Alcohol dehydrogenase class-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11766
Assay: GSNOR Assay: GSNO and Enzyme/NADH Solutions are made up fresh each day. The Solutions are filtered and allowed to warm to room temperature. GSNO Solution: 100 mM NaPO4 (pH 7.4), 0.480 mM GSNO. 396 μL of GSNO Solution is added to a cuvette followed by 8 μL of test compound in DMSO (or DMSO only for full reaction control) and mixed with the pipette tip. Compounds to be tested are made up at a stock concentration of 10 mM in 100% DMSO. 2 fold serial dilutions are done in 100% DMSO. 8 μL of each dilution are added to an assay so that the final concentration of DMSO in the assay is 1%. The concentrations of compounds tested range from 100 to 0.003 μM. Enzyme/NADH Solution: 100 mM NaPO4 (pH 7.4), 0.600 mM NADH, 1.0 μg/mL GSNO Reductase. 396 μL of the Enzyme/NADH Solution is added to the cuvette to start the reaction.
Measurement: IC50 = 3170 nM (pChEMBL 5.5)
Descriptors: MW 437.48, ALogP 3.98, HBA 6, HBD 3, PSA 121.11, QED 0.54
Compound (SMILES): CCOc1cc([C@@H]2NC(=O)N=C(c3cccnc3)C2c2ccsc2)cc(C(=O)O)c1O
InChIKey: LBQQJPUROPEYKE-NNBQYGFHSA-N
Target: Alcohol dehydrogenase class-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11766
Assay: GSNOR Assay: GSNO and Enzyme/NADH Solutions are made up fresh each day. The Solutions are filtered and allowed to warm to room temperature. GSNO Solution: 100 mM NaPO4 (pH 7.4), 0.480 mM GSNO. 396 μL of GSNO Solution is added to a cuvette followed by 8 μL of test compound in DMSO (or DMSO only for full reaction control) and mixed with the pipette tip. Compounds to be tested are made up at a stock concentration of 10 mM in 100% DMSO. 2 fold serial dilutions are done in 100% DMSO. 8 μL of each dilution are added to an assay so that the final concentration of DMSO in the assay is 1%. The concentrations of compounds tested range from 100 to 0.003 μM. Enzyme/NADH Solution: 100 mM NaPO4 (pH 7.4), 0.600 mM NADH, 1.0 μg/mL GSNO Reductase. 396 μL of the Enzyme/NADH Solution is added to the cuvette to start the reaction.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 437.48, ALogP 3.98, HBA 6, HBD 3, PSA 121.11, QED 0.54