lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Nc1cncc(-c2ccc3cc(NC(=O)C4CC4)ncc3c2)c1
InChIKey: DNVLGHPONZRHTO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 304.35, ALogP 3.23, HBA 4, HBD 2, PSA 80.9, QED 0.78
Compound (SMILES): Nc1cc(-c2ccc3cc(NC(=O)C4CC4)ncc3c2)ccn1
InChIKey: MMGQYZCZIXXUSA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 304.35, ALogP 3.23, HBA 4, HBD 2, PSA 80.9, QED 0.78
Compound (SMILES): CC(C)=Cc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: SXXYOARNHDMKNZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 266.34, ALogP 4.01, HBA 2, HBD 1, PSA 41.99, QED 0.91
Compound (SMILES): Cc1cc(Cl)ncc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: HKNJEQQBOZBONO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 337.81, ALogP 4.61, HBA 3, HBD 1, PSA 54.88, QED 0.71
Compound (SMILES): O=C(Nc1cc2ccc(-c3cnccc3Cl)cc2cn1)C1CC1
InChIKey: DJLTWWLCRCCXGH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.07 nM (pChEMBL 10.149999618530273)
Descriptors: MW 323.78, ALogP 4.3, HBA 3, HBD 1, PSA 54.88, QED 0.78
Compound (SMILES): CC(C)Cc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: ZHRSVMMWEDNZEX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 268.36, ALogP 3.78, HBA 2, HBD 1, PSA 41.99, QED 0.92
Compound (SMILES): Cn1ncc2c(-c3ccc4cc(NC(=O)C5CC5)ncc4c3)cccc21
InChIKey: VDZFOKTZABDMRV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 342.4, ALogP 4.14, HBA 4, HBD 1, PSA 59.81, QED 0.61
Compound (SMILES): O=C1Cc2c(cccc2-c2ccc3cc(NC(=O)C4CC4)ncc3c2)N1
InChIKey: XBXYJNVDIOQSHF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 343.39, ALogP 3.74, HBA 3, HBD 2, PSA 71.09, QED 0.76
Compound (SMILES): Cc1c(F)cncc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: GSLMJIPSSNUWRV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.02 nM (pChEMBL 10.699999809265137)
Descriptors: MW 321.36, ALogP 4.09, HBA 3, HBD 1, PSA 54.88, QED 0.79
Compound (SMILES): Cc1ccc(F)cc1-c1ccc2cc(NC(=O)C3CC3c3ccccc3)ncc2c1
InChIKey: JWWCMICUHVKSSU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 396.47, ALogP 6.09, HBA 2, HBD 1, PSA 41.99, QED 0.45
Compound (SMILES): Cc1cc(CO)cc(Nc2cc3ccc(-c4cc(F)ccc4C)cc3cn2)n1
InChIKey: SFAMJFCDXZDVKN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 373.43, ALogP 5.29, HBA 4, HBD 2, PSA 58.04, QED 0.51
Compound (SMILES): Cc1cc(C(C)(C)O)cc(Nc2cc3ccc(-c4cc(F)ccc4C)cc3cn2)n1
InChIKey: VITQLWFDDMWUOS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 401.49, ALogP 6.02, HBA 4, HBD 2, PSA 58.04, QED 0.44
Compound (SMILES): Cc1cc(N)ncc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: GNPHAZATVBAUTM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 318.38, ALogP 3.54, HBA 4, HBD 2, PSA 80.9, QED 0.77
Compound (SMILES): Cc1ccncc1-c1ccc2cc(Nc3cc(CO)ccn3)ncc2c1
InChIKey: DBMYDXZBGMGPNE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 342.4, ALogP 4.24, HBA 5, HBD 2, PSA 70.93, QED 0.58
Compound (SMILES): Cc1ncc(CO)cc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: UYFKVUDXPPBSNI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 333.39, ALogP 3.45, HBA 4, HBD 2, PSA 75.11, QED 0.77
Compound (SMILES): COc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: MYLORPHKQFZJID-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 242.28, ALogP 2.59, HBA 3, HBD 1, PSA 51.22, QED 0.9
Compound (SMILES): C[C@@H](CO)Oc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: VYVBIQYZCBIUEY-JTQLQIEISA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 286.33, ALogP 2.34, HBA 4, HBD 2, PSA 71.45, QED 0.88
Compound (SMILES): CC(C)(CO)Oc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: TTXRSZTUJKVNSM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 300.36, ALogP 2.73, HBA 4, HBD 2, PSA 71.45, QED 0.89
Compound (SMILES): Cc1ccc(C(C)O)cc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: LWGDHQMVWAURIP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 346.43, ALogP 4.61, HBA 3, HBD 2, PSA 62.22, QED 0.72
Compound (SMILES): O=C(Nc1cc2ccc(-c3cccc(CO)c3)cc2cn1)C1CC1
InChIKey: WAVQTBRBDYGQSJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 318.38, ALogP 3.74, HBA 3, HBD 2, PSA 62.22, QED 0.77
Compound (SMILES): O=C(Nc1cc2ccc(-c3cc(CO)ccc3Cl)cc2cn1)C1CC1
InChIKey: AAKVCHBQVYHBAI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 352.82, ALogP 4.4, HBA 3, HBD 2, PSA 62.22, QED 0.73
Compound (SMILES): O=C(Nc1cc2ccc(-c3cc(CO)ccc3F)cc2cn1)C1CC1
InChIKey: PAUYVUICCGGMJK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 336.37, ALogP 3.88, HBA 3, HBD 2, PSA 62.22, QED 0.76
Compound (SMILES): CCOc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: LCKAZURGBSUWHW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 256.3, ALogP 2.98, HBA 3, HBD 1, PSA 51.22, QED 0.91
Compound (SMILES): O=C(Nc1cc2ccc(OCCO)cc2cn1)C1CC1
InChIKey: ZDYWOXWREXEEMO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 272.3, ALogP 1.95, HBA 4, HBD 2, PSA 71.45, QED 0.87
Compound (SMILES): CC(CO)Cc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: OHDAQYLVBQIISH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 284.36, ALogP 2.75, HBA 3, HBD 2, PSA 62.22, QED 0.89
Compound (SMILES): C[C@H](CO)Oc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: VYVBIQYZCBIUEY-SNVBAGLBSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 286.33, ALogP 2.34, HBA 4, HBD 2, PSA 71.45, QED 0.88
Compound (SMILES): COC[C@H](C)Oc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: KPTCSPNLFCRABU-NSHDSACASA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 300.36, ALogP 3, HBA 4, HBD 1, PSA 60.45, QED 0.89
Compound (SMILES): Cc1ccc(F)cc1-c1ccc2cc(NC(=O)C3C[C@@H]3C)ncc2c1
InChIKey: BKDVILNWHYFSDN-YTJLLHSVSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 334.39, ALogP 4.94, HBA 2, HBD 1, PSA 41.99, QED 0.74
Compound (SMILES): Cc1ccc(F)cc1-c1ccc2cc(NC(=O)C3C[C@H]3C)ncc2c1
InChIKey: BKDVILNWHYFSDN-BSOCMFCZSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 334.39, ALogP 4.94, HBA 2, HBD 1, PSA 41.99, QED 0.74
Compound (SMILES): Cc1ccc(NC(=O)c2cnn(C)c2)cc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: YAFJUUKGVWNFEJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 425.49, ALogP 4.54, HBA 5, HBD 2, PSA 88.91, QED 0.49
Compound (SMILES): O=C(Nc1cc2ccc(-c3cccnc3CO)cc2cn1)C1CC1
InChIKey: MEQSHNONPDKEST-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 319.36, ALogP 3.14, HBA 4, HBD 2, PSA 75.11, QED 0.77
Compound (SMILES): Cc1cc(C(=O)Nc2ccc(C)c(-c3ccc4cc(NC(=O)C5CC5)ncc4c3)c2)ccn1
InChIKey: BSJBORQAKJLNPL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 436.52, ALogP 5.51, HBA 4, HBD 2, PSA 83.98, QED 0.43
Compound (SMILES): Cc1ccc(NC(=O)C2CCOCC2)cc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: NDEMINNZPGRSCE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 429.52, ALogP 4.92, HBA 4, HBD 2, PSA 80.32, QED 0.6
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: ZOVAXVYMZMRSJU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 489.5, ALogP 6.83, HBA 3, HBD 2, PSA 71.09, QED 0.32
Compound (SMILES): Cc1ccc(NC(=O)C2CCN(C)CC2)cc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: HBJSLQIMDLCXPI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 442.56, ALogP 4.84, HBA 4, HBD 2, PSA 74.33, QED 0.59
Compound (SMILES): Cc1ccc(NC(=O)c2ccc(CN(C)C)cc2)cc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: BSUVWQXRZDHLFO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 478.6, ALogP 5.87, HBA 4, HBD 2, PSA 74.33, QED 0.35
Compound (SMILES): Cc1c(N)cncc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: LTRWEJFGLYDZMJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.09 nM (pChEMBL 10.050000190734863)
Descriptors: MW 318.38, ALogP 3.54, HBA 4, HBD 2, PSA 80.9, QED 0.77
Compound (SMILES): Cc1c(O)cncc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: PPRGYPQAEDMVCJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.04 nM (pChEMBL 10.399999618530273)
Descriptors: MW 319.36, ALogP 3.66, HBA 4, HBD 2, PSA 75.11, QED 0.77
Compound (SMILES): Cc1cc(CO)ncc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: DZGNQTIIEFDOMN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.02 nM (pChEMBL 10.699999809265137)
Descriptors: MW 333.39, ALogP 3.45, HBA 4, HBD 2, PSA 75.11, QED 0.77
Compound (SMILES): Cc1ccnc(CO)c1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: FMCNJEWIGMRIMB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.07 nM (pChEMBL 10.149999618530273)
Descriptors: MW 333.39, ALogP 3.45, HBA 4, HBD 2, PSA 75.11, QED 0.77
Compound (SMILES): O=C(Nc1cc2ccc(N3CCC(O)C3)cc2cn1)C1CC1
InChIKey: ONUNOOGKYPRZDG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 297.36, ALogP 2.15, HBA 4, HBD 2, PSA 65.46, QED 0.91
Compound (SMILES): NCc1cccc(-c2ccc3cc(NC(=O)C4CC4)ncc3c2)c1
InChIKey: MDBVZTFIVLWGDQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 317.39, ALogP 3.71, HBA 3, HBD 2, PSA 68.01, QED 0.77
Compound (SMILES): Cc1c(CO)cncc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: VCYDROHQLPAYQX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 333.39, ALogP 3.45, HBA 4, HBD 2, PSA 75.11, QED 0.77
Compound (SMILES): CC(C)(C)Oc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: KIJVLZLFJNILEW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 284.36, ALogP 3.76, HBA 3, HBD 1, PSA 51.22, QED 0.93
Compound (SMILES): Cc1ccc(NC(=O)c2ccc(C(C)N(C)C)cc2)cc1-c1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: KETKUILYCSNHBK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 492.62, ALogP 6.43, HBA 4, HBD 2, PSA 74.33, QED 0.31
Compound (SMILES): Cc1ccncc1-c1ccc2cc(Nc3cccc(CO)n3)ncc2c1
InChIKey: BYDLBOFYBRXPRU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 342.4, ALogP 4.24, HBA 5, HBD 2, PSA 70.93, QED 0.58
Compound (SMILES): COC[C@@H](C)Oc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: KPTCSPNLFCRABU-LLVKDONJSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 300.36, ALogP 3, HBA 4, HBD 1, PSA 60.45, QED 0.89
Compound (SMILES): C[C@H](CCO)Oc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: AZVVAMVNOBVYEO-LLVKDONJSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 300.36, ALogP 2.73, HBA 4, HBD 2, PSA 71.45, QED 0.86
Compound (SMILES): O=C(Nc1cc2ccc(OC3CCC3)cc2cn1)C1CC1
InChIKey: QSMHHMSWCWISIX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 282.34, ALogP 3.51, HBA 3, HBD 1, PSA 51.22, QED 0.93
Compound (SMILES): O=C(Nc1cc2ccc(-c3cnccc3CO)cc2cn1)C1CC1
InChIKey: ICAPSJXNOGXIGH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 319.36, ALogP 3.14, HBA 4, HBD 2, PSA 75.11, QED 0.77
Compound (SMILES): C[C@H](CNC(=O)c1ccc(CN2CCN(C)CC2)cc1)Cc1ccc2cc(NC(=O)C3CC3)ncc2c1
InChIKey: OEHCIBWJPZUGDE-NRFANRHFSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 499.66, ALogP 3.94, HBA 5, HBD 2, PSA 77.57, QED 0.47
Compound (SMILES): COc1ccc2c(c1)[C@]13CCN(CC4CC4)[C@H](C2)[C@]1(O)C[C@H](CC(=O)O)C(=O)C3
InChIKey: QMPGKHYVAFTWNZ-DQOBCGMHSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand dose-Displacement Binding Assay: Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 μg membrane protein (recombinant κ opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 μl binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 μM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 hour at a temperature of about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Perkin Elmer, Shelton, Conn.) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by five filtration washes with 200 μl ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 1-2 hours. Fifty μl/well scintillation cocktail (Perkin Elmer, Shelton, Conn.) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 260.85 nM (pChEMBL 6.579999923706055)
Descriptors: MW 399.49, ALogP 2.16, HBA 5, HBD 2, PSA 87.07, QED 0.79
Compound (SMILES): O=S(=O)(c1ccc(-c2ccc3[nH]nc(-c4cc(N5CCOCC5)ncn4)c3c2)cc1)N1CCCC1
InChIKey: RUKZRYWFYTWYAQ-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: LanthaScreen™ Assay (5 mM ATP): a) 400 nl of a 1:2.15 serial dilution of test compound(98 μM top assay concentration) is spotted via Labcyte Echo to certain wells in a 384 well black, untreated plate. Control wells contain 400 nl of either DMSO or 400 nl of a known inhibitor in DMSO. b) 10 μl of a 2.5 nM LRRK2(G2019S mutation, GST-LRRK2(amino acids 970-2527)) enzyme solution in 1× assay buffer(50 mM Tris pH 8.5, 10 mM MgCl2, 0.01% Brij-35, 1.0 mM EGTA, 2 mM DTT, 0.05 mM NaVO4) is added to all wells. c) A 30 minute room temperature incubation is followed by addition of 10 μl of 800 nM fluorescein labeled LRRKtide peptide substrate and 10 mM ATP solution in 1× assay buffer to all wells. d) After a 35 minute room temperature incubation, 20 μl of TR-FRET Dilution Buffer(Invitrogen PV3756B) containing 4 nM Tb-labeled anti-phospho LRRKtide antibody and 20 mM EDTA is added to all wells. e) Plates are incubated at room temperature for 1 hour and read on an Envision™ multi-mode plate reader with LanthaScreen™ settings. Results are analysed using Assay Data Analyzer.
Measurement: IC50 = 914.4 nM (pChEMBL 6.039999961853027)
Descriptors: MW 490.59, ALogP 3.31, HBA 7, HBD 1, PSA 104.31, QED 0.46
Compound (SMILES): O=C(NCc1c[nH]nn1)c1cc(NC(=O)c2cc(-c3ccc(F)cn3)c(F)cc2Cl)n(-c2ccccc2)n1
InChIKey: PGLNLJGOMCQXAQ-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Cell Based Assay: TRKA co-expressed with p75: The assays are based upon DiscoveRx's proprietary Enzyme Fragment Complementation (EFC) technology. In the case of the TRK cell lines, the enzyme acceptor (EA) protein is fused to a SH2 protein and the TRK receptor of interest has been tagged with a Prolink tag. Cryopreserved PathHunter cells are used from either in-house produced batches or bulk batches bought directly from DiscoveRx. Cryopreserved cells are resuscitated, spun 1000 rpm for 4 min to remove freezing media, and resuspended in MEM+0.5% horse serum (both Invitrogen) to 5e^5 cells/ml. The cells are then plated using a Multidrop into Greiner white tissue culture treated plates at 20 μl/well and incubated for 24 h at 37 °C., 5% CO2, high humidity. On the day of the assay, the cell plates are allowed to cool to room temperature for 30 min prior to the assay. 4 mM stock solutions of test compounds are prepared and serially diluted in 100% DMSO. A standard curve using the compound of Example 135, WO2005/116035 at a top concentration of 150 μM is also prepared on each test plate. High percentage effect (HPE) is defined by 150 μM of the compound of Example 135, WO2005/116035 and 0% effect (ZPE) is defined by 100% DMSO. Plates containing 1 μl of serially diluted compound, standard and HPE/ZPE are diluted 1/66 in assay buffer (PBS minus Ca2+, minus Mg2+ with 0.05% pluronic F127) using a Wellmate. Using a Platemate Plus, 5 μl of 1/66 diluted test compounds is then transferred to the cell plate and allowed to reach equilibrium by incubating for 30 min at room temperature before addition of agonist stimulus: 10 μl/well of 2 nM (0.571 nM FAC) of the cognate neurotrophin (Peprotech) diluted in agonist buffer (HBSS with 0.25% BSA). Final assay concentration of the test compounds is 8.66 μM, (the compound of Example 135, WO2005/116035 FAC is 0.325 μM). The plates are left at room temperature for a further 2 hours before addition of 10 μl of the DiscoveRx PathHunter detection reagent (made up by adding 1 part Galacton Star, 5 parts Emerald II and 19 parts Cell Assay Buffer as per the manufacturer's instructions). After reagent addition, plates are covered and incubated at room temperature for 60 minutes. Luminescence signal is read using an Envision.
Measurement: IC50 = 18.95 nM (pChEMBL 7.71999979019165)
Descriptors: MW 534.91, ALogP 4.17, HBA 7, HBD 3, PSA 130.48, QED 0.29
Compound (SMILES): CN(C)CCCOc1cccc(-c2n[nH]c3ccc(-c4nnn[nH]4)cc23)c1
InChIKey: QIZHAKZFDHTVCE-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P45984
Assay: Inhibition of His6-tagged JNK2 (unknown origin) assessed as reduction in c-Jun phosphorylation using GST-c-Jun (1 to 79 residues) and [gamma32P]ATP incubated for 1 hr by scintillation counting assay
Measurement: IC50 <= 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 363.43, ALogP 2.74, HBA 6, HBD 2, PSA 95.61, QED 0.49
Compound (SMILES): O=C1NC2(CCCC2)C(=O)N[C@@H](Cc2ccccc2)C(=O)NC/C=C\c2ccccc2OCCN[C@H]1Cc1cccs1
InChIKey: QWXCEHMYOPLRBB-AQVRRDMNSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Displacement of [125I]-Ghrelin from human GSHR1a transfected in HEK293 cell membranes after 30 mins by microplate scintillation and luminescence counting method
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 586.76, ALogP 3.63, HBA 6, HBD 4, PSA 108.56, QED 0.37
Compound (SMILES): COC(=O)c1ccc(S(=O)(=O)N(CCCC(F)(F)F)c2sc3ccccc3c2C)cc1
InChIKey: XYLIMBSVDFDZEB-UHFFFAOYSA-N
Target: Transient receptor potential M8 protein (SINGLE PROTEIN), Canis lupus familiaris
UniProt: Q1A7N1
Assay: Functional Assay: The functional activity of compounds of the formula (I) was determined by measuring changes in intracellular calcium concentration using a Ca2+-sensitive fluorescent dye. The changes in fluorescent signal were monitored by a fluorescence plate reader, either a FLIPR (Molecular Devices) or FDSS (Hamamatsu). Increases in intracellular Ca2+ concentration were readily detected upon activation with icilin.At 24 hrs prior to assay, HEK293 cells stably expressing canine TRPM8 were seeded in culture medium in black wall, clear-base poly-D-lysine coated 384-well plates (BD Biosciences, NJ, USA) and grown overnight in 5% CO2 at 37° C. On assay day, growth media was removed and cells were loaded with Calcium 3 Dye (Molecular Devices) for 35 min at 37° C., under 5% CO2 and then for 25 min at room temperature and atmosphere. Subsequently, cells were tested for agonist-induced increases in intracellular Ca2+ levels using FLIPR or FDSS. Cells were challenged with a compound of the Formula (I) (at varying concentrations) and intracellular Ca2+ was measured for 5 min prior to the addition of icilin to all wells to achieve a final concentration that produces approximately an 80% maximal response. EC50 or IC50 values for compounds of the present invention were determined from eight-point dose-response studies.
Measurement: IC50 = 35.6 nM (pChEMBL 7.449999809265137)
Descriptors: MW 471.52, ALogP 5.53, HBA 5, HBD 0, PSA 63.68, QED 0.42
Compound (SMILES): Cc1cc(C)n2nc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(Cl)c3)nc2n1
InChIKey: ZTSRQAIVDNBPLK-UHFFFAOYSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Representative compounds were serially diluted in dimethyl sulfoxide (DMSO) starting at 50 uM (2x starting concentration; 10% DMSO) and 10 uL were transferred into a 384-well plate. Then 10 uL of a protein/probe/antibody mix was added to each well at final concentrations listed in TABLE 1. The samples are then mixed on a shaker for 1 minute and incubated for an additional 3 hours at room temperature. For each assay, the probe/antibody and protein/probe/antibody were included on each assay plate as negative and positive controls, respectively. Fluorescence was measured on the ENVISION plate reader (Perkin Elmer) using a 340/35 nm excitation filter and 520/525 (F-Bak peptide) and 495/510 nm (Tb-labeled anti-Histidine antibody) emission filters Inhibition constants (Ki) are shown in TABLE 2 below and were determined using Wang's equation (Wang Z.-X. An Exact Mathematical Expression For Describing Competitive Binding Of Two Different Ligands To A Protein Molecule. FEBS Lett. 1995, 360:111-4).
Measurement: Ki = 0.407 nM (pChEMBL 9.390000343322754)
Descriptors: MW 774.77, ALogP 7.74, HBA 10, HBD 1, PSA 122.03, QED 0.16