lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccncc1-c1cc2cnc(NC(=O)C3CC3F)cc2cn1
InChIKey: SUDZSZXCDIIYET-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 = 0.434 nM (pChEMBL 9.359999656677246)
Descriptors: MW 322.34, ALogP 3.3, HBA 4, HBD 1, PSA 67.77, QED 0.8
Compound (SMILES): Cc1cc([C@@H](N)C(F)(F)F)ncc1-c1ccc2cc(NC(=O)C3C[C@@H]3F)ncc2c1
InChIKey: JTMLSGGBBKYZLY-WHJCRDCLSA-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 = 1.75 nM (pChEMBL 8.760000228881836)
Descriptors: MW 418.39, ALogP 4.46, HBA 4, HBD 2, PSA 80.9, QED 0.61
Compound (SMILES): Cc1cc([C@H](N)C(F)(F)F)ncc1-c1ccc2cc(NC(=O)C3C[C@@H]3F)ncc2c1
InChIKey: JTMLSGGBBKYZLY-LEKXZLICSA-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 = 1.75 nM (pChEMBL 8.760000228881836)
Descriptors: MW 418.39, ALogP 4.46, HBA 4, HBD 2, PSA 80.9, QED 0.61
Compound (SMILES): CCO[C@@H]1CC1C(=O)Nc1cc2ccc(-c3cnccc3C)cc2cn1
InChIKey: MMVLDNJVKIMPTF-WHCXFUJUSA-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 = 0.45 nM (pChEMBL 9.350000381469727)
Descriptors: MW 347.42, ALogP 3.97, HBA 4, HBD 1, PSA 64.11, QED 0.76
Compound (SMILES): CCO[C@H]1CC1C(=O)Nc1cc2ccc(-c3cnccc3C)cc2cn1
InChIKey: MMVLDNJVKIMPTF-NNBQYGFHSA-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 = 0.45 nM (pChEMBL 9.350000381469727)
Descriptors: MW 347.42, ALogP 3.97, HBA 4, HBD 1, PSA 64.11, QED 0.76
Compound (SMILES): Cc1ccnc([C@@H](C)O)c1-c1ccc2cc(NC(=O)C3C[C@@H]3F)ncc2c1
InChIKey: PZTMYTIVXKJTBY-PWBPUHETSA-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 = 0.246 nM (pChEMBL 9.609999656677246)
Descriptors: MW 365.41, ALogP 3.96, HBA 4, HBD 2, PSA 75.11, QED 0.73
Compound (SMILES): Cc1ccnc([C@@H](O)C(F)(F)F)c1-c1ccc2cc(NC(=O)C3C[C@@H]3F)ncc2c1
InChIKey: XONWSRGXWACTJV-DZNRSUDRSA-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 = 0.265 nM (pChEMBL 9.579999923706055)
Descriptors: MW 419.38, ALogP 4.5, HBA 4, HBD 2, PSA 75.11, QED 0.61
Compound (SMILES): Cc1ccnc([C@H](O)C(F)(F)F)c1-c1ccc2cc(NC(=O)C3C[C@@H]3F)ncc2c1
InChIKey: XONWSRGXWACTJV-KDBUZZBASA-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 = 0.265 nM (pChEMBL 9.579999923706055)
Descriptors: MW 419.38, ALogP 4.5, HBA 4, HBD 2, PSA 75.11, QED 0.61
Compound (SMILES): Cc1ccnc([C@H](C)O)c1-c1ccc2cc(NC(=O)C3C[C@@H]3F)ncc2c1
InChIKey: PZTMYTIVXKJTBY-VUOHQMJNSA-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 = 0.246 nM (pChEMBL 9.609999656677246)
Descriptors: MW 365.41, ALogP 3.96, HBA 4, HBD 2, PSA 75.11, QED 0.73
Compound (SMILES): Cc1cc([C@H](O)C(F)(F)F)ncc1-c1ccc2cc(NC(=O)C(C)C)ncc2c1
InChIKey: VAGKNGZZTCJYNV-IBGZPJMESA-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 = 3.46 nM (pChEMBL 8.460000038146973)
Descriptors: MW 403.4, ALogP 4.8, HBA 4, HBD 2, PSA 75.11, QED 0.66
Compound (SMILES): Cc1cc([C@@H](O)C(F)(F)F)ncc1-c1ccc2cc(NC(=O)C(C)C)ncc2c1
InChIKey: VAGKNGZZTCJYNV-LJQANCHMSA-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 = 3.46 nM (pChEMBL 8.460000038146973)
Descriptors: MW 403.4, ALogP 4.8, HBA 4, HBD 2, PSA 75.11, QED 0.66
Compound (SMILES): C[C@@H]1CCC(=O)N1c1ccc2cc(NC(=O)C3C[C@@H]3F)ncc2c1
InChIKey: WRGQMIQWFKFVTM-PYUGYUQBSA-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 = 0.0799 nM (pChEMBL 10.100000381469727)
Descriptors: MW 327.36, ALogP 3.05, HBA 3, HBD 1, PSA 62.3, QED 0.94
Compound (SMILES): C[C@H]1CCC(=O)N1c1ccc2cc(NC(=O)C3C[C@@H]3F)ncc2c1
InChIKey: WRGQMIQWFKFVTM-WAJWKUKPSA-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 = 0.0799 nM (pChEMBL 10.100000381469727)
Descriptors: MW 327.36, ALogP 3.05, HBA 3, HBD 1, PSA 62.3, QED 0.94
Compound (SMILES): COc1cc2cnc(C(O)(c3cnn[nH]3)C(C)C)cc2cc1OC
InChIKey: FNQBQSDVRFAVIN-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: In the design of clinically safe and effective metalloenzyme inhibitors, use of the most appropriate metal-binding group for the particular target and clinical indication is critical. If a weakly binding metal-binding group is utilized, potency may be suboptimal. On the other hand, if a very tightly binding metal-binding group is utilized, selectivity for the target enzyme versus related metalloenzymes may be suboptimal. The lack of optimal selectivity can be a cause for clinical toxicity due to unintended inhibition of these off-target metalloenzymes. One example of such clinical toxicity is the unintended inhibition of human drug metabolizing enzymes such as CYP2C9, CYP2C19 and CYP3A4 by the currently-available prostate anticancer agent ketoconazole. It is believed that this off-target inhibition is caused primarily by the indiscriminate binding of the currently utilized 1-imidazole to iron in the active site of CYP2C9, CYP2C19 and CYP3A4.
Measurement: IC50 = 23000 nM (pChEMBL 4.639999866485596)
Descriptors: MW 328.37, ALogP 2.26, HBA 6, HBD 2, PSA 93.15, QED 0.75
Compound (SMILES): O=C(/C=C/c1ccc2nc(CCc3ccccc3)c(Nc3ccc4c(c3)OCO4)n2c1)NO
InChIKey: RDOWSBWCNULCQW-MDWZMJQESA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: BIOMOL Fluorescent-Based Assay: The assay has been carried out in 96 well format and the BIOMOL fluorescent-based HDAC activity assay has been applied. The reaction composed of assay buffer, containing 25 mM Tris pH 7.5, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 1 mg/ml BSA, tested compounds, an appropriate concentration of HDAC1 enzyme, 500 uM Flur de lys generic substrate for HDAC1 enzyme and subsequently was incubated at room temperature for 2 h. Flur de lys Developer was added and the reaction was incubated for 10 min. Briefly, deacetylation of the substrate sensitizes it to the developer, which then generates a fluorophore. The fluorophore is excited with 360 nm light and the emitted light (460 nm) is detected on a fluorometric plate reader (Tecan Ultra Microplate detection system, Tecan Group Ltd.).
Measurement: IC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 442.48, ALogP 4.11, HBA 7, HBD 3, PSA 97.12, QED 0.23
Compound (SMILES): CCCCN(C)Cc1c(-c2ccccc2)nc2cc(/C=C/C(=O)NO)ccn12
InChIKey: KXHFDCDZERKBKT-ZHACJKMWSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: BIOMOL Fluorescent-Based Assay: The assay has been carried out in 96 well format and the BIOMOL fluorescent-based HDAC activity assay has been applied. The reaction composed of assay buffer, containing 25 mM Tris pH 7.5, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 1 mg/ml BSA, tested compounds, an appropriate concentration of HDAC1 enzyme, 500 uM Flur de lys generic substrate for HDAC1 enzyme and subsequently was incubated at room temperature for 2 h. Flur de lys Developer was added and the reaction was incubated for 10 min. Briefly, deacetylation of the substrate sensitizes it to the developer, which then generates a fluorophore. The fluorophore is excited with 360 nm light and the emitted light (460 nm) is detected on a fluorometric plate reader (Tecan Ultra Microplate detection system, Tecan Group Ltd.).
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 378.48, ALogP 3.75, HBA 5, HBD 2, PSA 69.87, QED 0.36
Compound (SMILES): CCCCc1nc2cc(/C=C/C(=O)NO)ccn2c1CN(CC)CC(C)CCC
InChIKey: HQAWIENKLMQWHU-VAWYXSNFSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: BIOMOL Fluorescent-Based Assay: The assay has been carried out in 96 well format and the BIOMOL fluorescent-based HDAC activity assay has been applied. The reaction composed of assay buffer, containing 25 mM Tris pH 7.5, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 1 mg/ml BSA, tested compounds, an appropriate concentration of HDAC1 enzyme, 500 uM Flur de lys generic substrate for HDAC1 enzyme and subsequently was incubated at room temperature for 2 h. Flur de lys Developer was added and the reaction was incubated for 10 min. Briefly, deacetylation of the substrate sensitizes it to the developer, which then generates a fluorophore. The fluorophore is excited with 360 nm light and the emitted light (460 nm) is detected on a fluorometric plate reader (Tecan Ultra Microplate detection system, Tecan Group Ltd.).
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 400.57, ALogP 4.45, HBA 5, HBD 2, PSA 69.87, QED 0.31
Compound (SMILES): CCN(CC)C(=O)c1c(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)cnn1C
InChIKey: PBAZUQBATARWOT-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 137.1 nM (pChEMBL 6.860000133514404)
Descriptors: MW 435.49, ALogP 2.36, HBA 9, HBD 2, PSA 130.82, QED 0.55
Compound (SMILES): Cc1ccc(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)c(C(=O)N(C)C)n1
InChIKey: KLOHLOQYPGBYBL-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 418.46, ALogP 2.55, HBA 8, HBD 2, PSA 125.89, QED 0.63
Compound (SMILES): CNC(=O)c1c(NC(=O)c2nc(C3CC3)cnc2Nc2cncnc2)cnn1CC1CCOC1
InChIKey: AWHBWQJKBCAUTC-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Scintillation Proximity Assay : PDE10 activity of the compounds of the present invention was determined using a Scintillation Proximity Assay (SPA)-based method similar to the one previously described (Fawcett, L. et al., Proc Natl Acad Sci USA (2000) 97(7):3702-3707). The human PDE10A full length assay was performed in 96-well micro titer plates. The reaction mixture of 50 μl contained 20 mM HEPES pH=7.5/10 mM MgCl2/0.05 mg/ml BSA (Sigma cat. # A-7906), 50 nM cGMP (Sigma, cat. # G6129) and 50 nM [3H]-cGMP (GE Healthcare, cat. # TRK392 S.A. 13.2 Ci/mmol), 3.75 ng/well PDE10A enzyme (Enzo Life Science, Lausen, Switzerland cat #SE-534) with or without a specific test compound.
Measurement: IC50 = 15.1 nM (pChEMBL 7.820000171661377)
Descriptors: MW 463.5, ALogP 1.73, HBA 10, HBD 3, PSA 148.84, QED 0.45
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(C)CC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: YTHUQGIGAIZNIM-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 519.65, ALogP 5.08, HBA 7, HBD 2, PSA 86.28, QED 0.37
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(C(=O)OC(C)(C)C)CC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: PDJFRJFTKGLDDM-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 233 nM (pChEMBL 6.630000114440918)
Descriptors: MW 605.74, ALogP 6.38, HBA 8, HBD 2, PSA 112.58, QED 0.26
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCNCC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: SZPKERXOPUWUPW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 505.63, ALogP 4.74, HBA 7, HBD 3, PSA 95.07, QED 0.35
Compound (SMILES): CCN1CCN(C2CCc3cc(C(=O)Nc4ccc(C)c(Nc5nccc(-c6cccnc6)n5)c4)ccc32)CC1
InChIKey: JVGNHFZOVWJKER-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 533.68, ALogP 5.47, HBA 7, HBD 2, PSA 86.28, QED 0.33
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(C(C)C)CC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: PZINVJUNZRLUIM-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 547.71, ALogP 5.86, HBA 7, HBD 2, PSA 86.28, QED 0.3
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(CCO)CC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: JXVHQHBMOSSYBX-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 549.68, ALogP 4.44, HBA 8, HBD 3, PSA 106.51, QED 0.3
Compound (SMILES): CC(=O)N1CCN(C2CCc3cc(C(=O)Nc4ccc(C)c(Nc5nccc(-c6cccnc6)n5)c4)ccc32)CC1
InChIKey: AJIVJAKIEIICSU-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 547.66, ALogP 4.99, HBA 7, HBD 2, PSA 103.35, QED 0.35
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(C)CC2)cc1Nc1nccc(-c2cncnc2)n1
InChIKey: IQOAIXAFDYRGNK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 520.64, ALogP 4.47, HBA 8, HBD 2, PSA 99.17, QED 0.38
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCC(N(C)C)C2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: PANUCCHSDROJBK-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 533.68, ALogP 5.47, HBA 7, HBD 2, PSA 86.28, QED 0.33
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CC[C@@H](N(C)C)C2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: PANUCCHSDROJBK-FIQOPJFZSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 533.68, ALogP 5.47, HBA 7, HBD 2, PSA 86.28, QED 0.33
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CC[C@@H]3N2CCN(C)CC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: YTHUQGIGAIZNIM-LJAQVGFWSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 519.65, ALogP 5.08, HBA 7, HBD 2, PSA 86.28, QED 0.37
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(C)CC2)cc1Nc1nccc(-c2ccncc2)n1
InChIKey: GMYQHOQOEQWZGN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 519.65, ALogP 5.08, HBA 7, HBD 2, PSA 86.28, QED 0.37
Compound (SMILES): CCCNC(=S)c1ccc(-n2ccc3ccccc32)s1
InChIKey: OSMMLDCYRLJBKD-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 300.45, ALogP 4.37, HBA 3, HBD 1, PSA 16.96, QED 0.72
Compound (SMILES): CCCNC(=O)c1ccc(N2CCCCC2)s1
InChIKey: KYRYAIBHJGHRFB-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 252.38, ALogP 2.88, HBA 3, HBD 1, PSA 32.34, QED 0.89
Compound (SMILES): CCCNC(=O)c1ccc(-n2cccn2)s1
InChIKey: SVKULENTQVNTFM-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 235.31, ALogP 2.07, HBA 4, HBD 1, PSA 46.92, QED 0.88
Compound (SMILES): CCCNC(=O)c1ccc(N2CCN(C)CC2)s1
InChIKey: JAWCIYWVQKUFOY-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 267.4, ALogP 1.64, HBA 4, HBD 1, PSA 35.58, QED 0.9
Compound (SMILES): CCCNC(=O)c1ccc(-n2c(C)nc3ccccc32)s1
InChIKey: KBBUJPFPTIFZBX-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 299.4, ALogP 3.54, HBA 4, HBD 1, PSA 46.92, QED 0.8
Compound (SMILES): Cc1nc2cc(F)ccc2n1-c1ccc(C(=O)NC2CC2)s1
InChIKey: ZMABOCMNPRSBGX-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 315.37, ALogP 3.43, HBA 4, HBD 1, PSA 46.92, QED 0.8
Compound (SMILES): C[C@@H](Cc1ccccn1)NC(=O)c1cccnc1Oc1ccc(C(=O)c2nc3ccccc3[nH]2)cc1
InChIKey: JELIDGFVCMSZCH-SFHVURJKSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.541 nM (pChEMBL 9.270000457763672)
Descriptors: MW 477.52, ALogP 4.74, HBA 6, HBD 2, PSA 109.86, QED 0.31
Compound (SMILES): Cc1ccc(-c2cccnc2Oc2ccc(Nc3nc4ccccc4s3)cc2)cn1
InChIKey: JRUSNWSHZKTZAE-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 2.87 nM (pChEMBL 8.539999961853027)
Descriptors: MW 410.5, ALogP 6.6, HBA 6, HBD 1, PSA 59.93, QED 0.35
Compound (SMILES): C[C@@H](Cc1ccc(F)cc1)NC(=O)c1cccnc1Oc1ccc(C(=O)c2nc3ccccc3[nH]2)cc1
InChIKey: FOSHITYJKMWOLO-SFHVURJKSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 494.53, ALogP 5.48, HBA 5, HBD 2, PSA 96.97, QED 0.28
Compound (SMILES): O=C(c1ccc(Oc2ncccc2[C@@H]2CCCO2)cc1)c1nc2ccccc2[nH]1
InChIKey: PYQKQNHBHYHJMF-FQEVSTJZSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 13.3 nM (pChEMBL 7.880000114440918)
Descriptors: MW 385.42, ALogP 4.83, HBA 5, HBD 1, PSA 77.1, QED 0.5
Compound (SMILES): O=C(c1ccc(Oc2ncccc2[C@@H]2CCOC2)cc1)c1nc2ccccc2[nH]1
InChIKey: RLULHYKXDSLNFG-MRXNPFEDSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.92 nM (pChEMBL 9.039999961853027)
Descriptors: MW 385.42, ALogP 4.49, HBA 5, HBD 1, PSA 77.1, QED 0.51
Compound (SMILES): O[C@@H]1CCC[C@H](c2cccnc2Oc2ccc(Nc3nc4ccccc4s3)cc2)C1
InChIKey: HHGBPGARRHXTDJ-FUHWJXTLSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 2.21 nM (pChEMBL 8.65999984741211)
Descriptors: MW 417.53, ALogP 6.25, HBA 6, HBD 2, PSA 67.27, QED 0.4
Compound (SMILES): O=C(c1ccc(Oc2ncccc2[C@@H]2CCC[C@H](O)C2)cc1)c1nc2ccccc2[nH]1
InChIKey: ULRZEXNCMHFJNG-MSOLQXFVSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.547 nM (pChEMBL 9.260000228881836)
Descriptors: MW 413.48, ALogP 5, HBA 5, HBD 2, PSA 88.1, QED 0.45
Compound (SMILES): C[C@]1(O)CCC[C@H](c2cccnc2Oc2ccc(Nc3nc4ccccc4s3)cc2)C1
InChIKey: UOVFGSVAEKZAFD-GKVSMKOHSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 3.82 nM (pChEMBL 8.420000076293945)
Descriptors: MW 431.56, ALogP 6.64, HBA 6, HBD 2, PSA 67.27, QED 0.37
Compound (SMILES): CN1C[C@H](c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4[nH]3)cc2)CC1=O
InChIKey: FVONZJMRTSGTPL-MRXNPFEDSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.0748 nM (pChEMBL 10.130000114440918)
Descriptors: MW 412.45, ALogP 3.93, HBA 5, HBD 1, PSA 88.18, QED 0.5
Compound (SMILES): c1cnc(Oc2ccc(Nc3nc4ccccc4s3)cc2)c([C@H]2CCOC2)c1
InChIKey: HEDHWRMJTFXNQL-HNNXBMFYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.865 nM (pChEMBL 9.0600004196167)
Descriptors: MW 389.48, ALogP 5.73, HBA 6, HBD 1, PSA 56.27, QED 0.47