lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(OCC2CCCO2)n1
InChIKey: XLPVPBJNIDNXTL-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 509.53, ALogP 3.63, HBA 8, HBD 2, PSA 97.84, QED 0.56
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(OCC2CCCCN2C)n1
InChIKey: ZCKUZYXKPTWCGK-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 536.6, ALogP 3.93, HBA 8, HBD 2, PSA 91.85, QED 0.52
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(OC2CCCN(C)C2)n1
InChIKey: JGBKEMZDTUHFHD-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 522.57, ALogP 3.54, HBA 8, HBD 2, PSA 91.85, QED 0.57
Compound (SMILES): COc1ccc(OC)c(CCOc2nc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3OC)ncc2C(F)(F)F)c1
InChIKey: SXXOMSYACCMPRJ-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 589.62, ALogP 4.71, HBA 9, HBD 2, PSA 107.07, QED 0.33
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(OCc2cccc(OC)c2OC)n1
InChIKey: WYUAAMOYSFWEPG-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 575.59, ALogP 4.67, HBA 9, HBD 2, PSA 107.07, QED 0.36
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(OCC2CCCCO2)n1
InChIKey: YKOSIMCZGRDDSR-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 523.56, ALogP 4.02, HBA 8, HBD 2, PSA 97.84, QED 0.54
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(OCC2CCCCC2)n1
InChIKey: CJDXKHSSBTYOGQ-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 225 nM (pChEMBL 6.650000095367432)
Descriptors: MW 521.58, ALogP 5.03, HBA 7, HBD 2, PSA 88.61, QED 0.5
Compound (SMILES): COC(=O)COc1nc(Nc2ccc(C(=O)NC3CCN(C)CC3)cc2OC)ncc1C(F)(F)F
InChIKey: OQUJTBPKZUSUGN-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 497.47, ALogP 2.62, HBA 9, HBD 2, PSA 114.91, QED 0.53
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Oc2ccccc2-c2cncs2)n1
InChIKey: UHAAWRQHRLLPFP-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 222 nM (pChEMBL 6.650000095367432)
Descriptors: MW 584.62, ALogP 5.99, HBA 9, HBD 2, PSA 101.5, QED 0.26
Compound (SMILES): COc1ncc(-c2ccccc2Oc2nc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3OC)ncc2C(F)(F)F)s1
InChIKey: WIEGDGUETMPIOA-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 614.65, ALogP 6, HBA 10, HBD 2, PSA 110.73, QED 0.23
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Oc2ccccc2-c2ccon2)n1
InChIKey: DANBJJPBOFDHRV-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 568.56, ALogP 5.52, HBA 9, HBD 2, PSA 114.64, QED 0.28
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)c(F)cc1Nc1ncc(C(F)(F)F)c(Oc2cc(C)ccc2C#N)n1
InChIKey: WHBGIVOLYXJCQK-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 161 nM (pChEMBL 6.789999961853027)
Descriptors: MW 558.54, ALogP 5.18, HBA 8, HBD 2, PSA 112.4, QED 0.38
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)c(F)cc1Nc1ncc(C(F)(F)F)c(Oc2cccc(C)c2C#N)n1
InChIKey: HPMBFZIPRNMYPQ-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 558.54, ALogP 5.18, HBA 8, HBD 2, PSA 112.4, QED 0.38
Compound (SMILES): COc1cc(C(=O)O)ccc1Nc1ncc(C(F)(F)F)c(Oc2cccc3c2N(C)C(=O)CC3)n1
InChIKey: FJVJQVYFQYMHIB-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 488.42, ALogP 4.65, HBA 7, HBD 2, PSA 113.88, QED 0.52
Compound (SMILES): COc1cc(C(=O)NCCN(C)C)ccc1Nc1ncc(C(F)(F)F)c(Oc2cccc3c2N(C)C(=O)CC3)n1
InChIKey: NSXCAPODZSJXHU-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 558.56, ALogP 4.24, HBA 8, HBD 2, PSA 108.92, QED 0.4
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Oc2ccccc2NS(C)(=O)=O)n1
InChIKey: FHYNMNAJFXUBKP-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 594.62, ALogP 4.24, HBA 9, HBD 3, PSA 134.78, QED 0.33
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Oc2cccc3c2CS(=O)(=O)N3)n1
InChIKey: LYLMKOCCIJLDCM-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 365 nM (pChEMBL 6.440000057220459)
Descriptors: MW 592.6, ALogP 4.12, HBA 9, HBD 3, PSA 134.78, QED 0.37
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Oc2ccccc2N(C)S(C)(=O)=O)n1
InChIKey: VQASYMPGACLNFT-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 608.64, ALogP 4.26, HBA 9, HBD 2, PSA 125.99, QED 0.37
Compound (SMILES): CCN(c1ccccc1Oc1nc(Nc2ccc(C(=O)NC3CCN(C)CC3)cc2OC)ncc1C(F)(F)F)S(C)(=O)=O
InChIKey: UIZFQPRQYBAJSU-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 622.67, ALogP 4.65, HBA 9, HBD 2, PSA 125.99, QED 0.33
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)c(F)cc1Nc1ncc(C(F)(F)F)c(Oc2ccccc2N(C)S(C)(=O)=O)n1
InChIKey: SMJSJTGZUYUEOX-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 626.63, ALogP 4.4, HBA 9, HBD 2, PSA 125.99, QED 0.33
Compound (SMILES): CCN(c1ccccc1Oc1nc(Nc2cc(F)c(C(=O)NC3CCN(C)CC3)cc2OC)ncc1C(F)(F)F)S(C)(=O)=O
InChIKey: XLKPLMDUGLTRAC-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 640.66, ALogP 4.79, HBA 9, HBD 2, PSA 125.99, QED 0.3
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Oc2c(Cl)cccc2NS(C)(=O)=O)n1
InChIKey: JYTGEOSYGPERDW-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 629.06, ALogP 4.89, HBA 9, HBD 3, PSA 134.78, QED 0.3
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Oc2ccc(Cl)cc2NS(C)(=O)=O)n1
InChIKey: ZENAVEGFQAMLKF-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 629.06, ALogP 4.89, HBA 9, HBD 3, PSA 134.78, QED 0.3
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Oc2cc(F)ccc2NS(C)(=O)=O)n1
InChIKey: ZXPHTEZZEUECNB-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 612.61, ALogP 4.37, HBA 9, HBD 3, PSA 134.78, QED 0.3
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Oc2cc(C)ccc2NS(C)(=O)=O)n1
InChIKey: PRJLSVKAGUDIRA-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 608.64, ALogP 4.54, HBA 9, HBD 3, PSA 134.78, QED 0.32
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)c(F)cc1Nc1ncc(C(F)(F)F)c(Oc2cccc3c2CS(=O)(=O)N3)n1
InChIKey: DETYLJYZESWNOJ-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 610.59, ALogP 4.26, HBA 9, HBD 3, PSA 134.78, QED 0.34
Compound (SMILES): COc1cc(C(=O)NC2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Oc2cccc(C)c2N(C)C(C)=O)n1
InChIKey: VXWOTYGJLIQDHS-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: DELFIA Assay: This test uses active PTK2 enzyme (Invitrogen Code PV3832) and poly-Glu-Tyr (4:1, Sigma P-0275) as the kinase substrate. The kinase activity is detected by means of the phosphorylation of the substrate in a DELFIA assay. The phosphorylated substrate is detected with the Europium-labelled phosphotyrosine antibody PY20 (Perkin Elmer, No.: AD0038). In order to determine concentration-activity curves with PTK2-inhibitors the compounds are serially diluted in 10% DMSO/H2O and 10 L of each dilution are dispensed per well in a 96-well microtitre plate (clear U-shaped base plate, Greiner No. 650101) (the inhibitors are tested in duplicates) and mixed with 10 L/well of PTK2 kinase (0.01 ug/well). PTK2 kinase is diluted accordingly beforehand with kinase dilution buffer (20 mM TRIS/HCl pH 7.5, 0.1 mM EDTA, 0.1 mM EGTA, 0.286 mM sodium orthovanadate, 10% glycerol with the addition of freshly prepared BSA (fraction V 1 mg/mL) and DTT (1 mM)).
Measurement: IC50 = 245 nM (pChEMBL 6.610000133514404)
Descriptors: MW 586.61, ALogP 5.16, HBA 8, HBD 2, PSA 108.92, QED 0.37
Compound (SMILES): Cc1nc(C)c(CNc2nc(OC[C@H]3C[C@@H]3c3ccccn3)nc(Cl)c2C)s1
InChIKey: MAFLAYQHEPPOKU-CABCVRRESA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology that is well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the following examples had activity in reference assays by exhibiting the ability to inhibit the hydrolysis of the phosphosphate ester bond of a cyclic nucleotide. In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence, and a reverse primer corresponding to nucleotides 2406-2413 of human PDE10A2.
Measurement: Ki = 0.019 nM (pChEMBL 10.720000267028809)
Descriptors: MW 415.95, ALogP 4.7, HBA 7, HBD 1, PSA 72.82, QED 0.56
Compound (SMILES): Cc1c(Cl)nc(OCCCc2ccc3ncccc3n2)nc1NCc1cnn(C)c1
InChIKey: CBLPKRFXTKSMQE-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology that is well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the following examples had activity in reference assays by exhibiting the ability to inhibit the hydrolysis of the phosphosphate ester bond of a cyclic nucleotide. In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence, and a reverse primer corresponding to nucleotides 2406-2413 of human PDE10A2.
Measurement: Ki = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 423.91, ALogP 3.74, HBA 8, HBD 1, PSA 90.64, QED 0.34
Compound (SMILES): Cc1c(Cl)nc(OC[C@@H]2C[C@H]2c2ccc3ncccc3n2)nc1NCc1cnn(C)c1
InChIKey: ZTRLAMWVWONPNK-JKSUJKDBSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology that is well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the following examples had activity in reference assays by exhibiting the ability to inhibit the hydrolysis of the phosphosphate ester bond of a cyclic nucleotide. In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence, and a reverse primer corresponding to nucleotides 2406-2413 of human PDE10A2.
Measurement: Ki = 0.019 nM (pChEMBL 10.720000267028809)
Descriptors: MW 435.92, ALogP 3.91, HBA 8, HBD 1, PSA 90.64, QED 0.44
Compound (SMILES): Cc1c(Cl)nc(OC[C@H]2C[C@@H]2c2ccccn2)nc1NCc1cnn(C)c1
InChIKey: KIYBJKHIYOZLEC-CABCVRRESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of MK499 from hERG
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 384.87, ALogP 3.36, HBA 7, HBD 1, PSA 77.75, QED 0.63
Compound (SMILES): COc1nc(OC[C@H]2C[C@@H]2c2ccc3ncccc3n2)nc(NCc2cnn(C)c2)c1C
InChIKey: DTVOGHZNBWTEJY-SJORKVTESA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology that is well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the following examples had activity in reference assays by exhibiting the ability to inhibit the hydrolysis of the phosphosphate ester bond of a cyclic nucleotide. In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence, and a reverse primer corresponding to nucleotides 2406-2413 of human PDE10A2.
Measurement: Ki = 0.17 nM (pChEMBL 9.770000457763672)
Descriptors: MW 431.5, ALogP 3.26, HBA 9, HBD 1, PSA 99.87, QED 0.45
Compound (SMILES): Cn1cc(CNc2cc(C#N)nc(OC[C@H]3C[C@@H]3c3ccccn3)n2)cn1
InChIKey: BOIMWZLQRYPHRX-ZBFHGGJFSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology that is well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the following examples had activity in reference assays by exhibiting the ability to inhibit the hydrolysis of the phosphosphate ester bond of a cyclic nucleotide. In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence, and a reverse primer corresponding to nucleotides 2406-2413 of human PDE10A2.
Measurement: Ki = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 361.41, ALogP 2.27, HBA 8, HBD 1, PSA 101.54, QED 0.69
Compound (SMILES): Cc1nc(C)c(CNc2nc(OCCc3ccccn3)nc(C#N)c2C)s1
InChIKey: HABILOQCORRULL-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology that is well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the following examples had activity in reference assays by exhibiting the ability to inhibit the hydrolysis of the phosphosphate ester bond of a cyclic nucleotide. In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence, and a reverse primer corresponding to nucleotides 2406-2413 of human PDE10A2.
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 380.48, ALogP 3.36, HBA 8, HBD 1, PSA 96.61, QED 0.67
Compound (SMILES): CSc1nc(OC[C@H]2C[C@@H]2c2ccccn2)nc(NCc2cnn(C)c2)c1C
InChIKey: XYAJWZAJFMLNKS-CVEARBPZSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology that is well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the following examples had activity in reference assays by exhibiting the ability to inhibit the hydrolysis of the phosphosphate ester bond of a cyclic nucleotide. In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence, and a reverse primer corresponding to nucleotides 2406-2413 of human PDE10A2.
Measurement: Ki = 0.17 nM (pChEMBL 9.770000457763672)
Descriptors: MW 396.52, ALogP 3.43, HBA 8, HBD 1, PSA 77.75, QED 0.46
Compound (SMILES): Cc1c(NCc2cnn(C)c2)nc(OC[C@H]2C[C@@H]2c2ccccn2)nc1N(C)C
InChIKey: DWNQQGFFUDWETP-SJORKVTESA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology that is well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the following examples had activity in reference assays by exhibiting the ability to inhibit the hydrolysis of the phosphosphate ester bond of a cyclic nucleotide. In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence, and a reverse primer corresponding to nucleotides 2406-2413 of human PDE10A2.
Measurement: Ki = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 393.5, ALogP 2.77, HBA 8, HBD 1, PSA 80.99, QED 0.63
Compound (SMILES): Cc1nc(C)c(CNc2nc(OC[C@H]3C[C@@H]3c3ccc4ncccc4n3)ncc2C)s1
InChIKey: QSAKVKNWBJXZLL-SJORKVTESA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology that is well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the following examples had activity in reference assays by exhibiting the ability to inhibit the hydrolysis of the phosphosphate ester bond of a cyclic nucleotide. In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence, and a reverse primer corresponding to nucleotides 2406-2413 of human PDE10A2.
Measurement: Ki = 0.058 nM (pChEMBL 10.239999771118164)
Descriptors: MW 432.55, ALogP 4.6, HBA 8, HBD 1, PSA 85.71, QED 0.46
Compound (SMILES): Cc1nc(C)c(CNc2nc(OC[C@H]3C[C@@H]3c3ccccn3)nc(-c3ncco3)c2C)s1
InChIKey: NJVUBRVWXMXQDX-SJORKVTESA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Fluorescence Polarization Assay: The activity of the compounds in accordance with the present invention as PDE10 inhibitors may be readily determined without undue experimentation using a fluorescence polarization (FP) methodology that is well known in the art (Huang, W., et al., J. Biomol Screen, 2002, 7: 215). In particular, the compounds of the following examples had activity in reference assays by exhibiting the ability to inhibit the hydrolysis of the phosphosphate ester bond of a cyclic nucleotide. In a typical experiment the PDE10 inhibitory activity of the compounds of the present invention was determined in accordance with the following experimental method. PDE10A2 was amplified from human fetal brain cDNA (Clontech, Mountain View, Calif.) using a forward primer corresponding to nucleotides 56-77 of human PDE10A2 (Accession No. AF127480, Genbank Identifier 4894716), containing a Kozak consensus sequence, and a reverse primer corresponding to nucleotides 2406-2413 of human PDE10A2.
Measurement: Ki = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 448.55, ALogP 4.7, HBA 9, HBD 1, PSA 98.85, QED 0.41