lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(-c2ccc3ncc4[nH]c(=O)n(Cc5ccccc5)c4c3n2)cn1
InChIKey: MYAWLPADHVWLNU-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 2.39 nM (pChEMBL 8.619999885559082)
Descriptors: MW 383.41, ALogP 3.39, HBA 6, HBD 1, PSA 85.69, QED 0.51
Compound (SMILES): COc1ccc(-c2ccc3ncc4[nH]c(=O)n([C@H]5CC[C@H](OCCO)CC5)c4c3n2)cn1
InChIKey: JFXLBGOSVVDUOC-WKILWMFISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 0.644 nM (pChEMBL 9.1899995803833)
Descriptors: MW 435.48, ALogP 2.84, HBA 8, HBD 2, PSA 115.15, QED 0.48
Compound (SMILES): COc1ccc(-c2ccc3ncc4[nH]c(=O)n([C@H]5CC[C@H](O)CC5)c4c3n2)cn1
InChIKey: YWKQALJDAFOFGE-HDJSIYSDSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 0.51 nM (pChEMBL 9.289999961853027)
Descriptors: MW 391.43, ALogP 2.82, HBA 7, HBD 2, PSA 105.92, QED 0.56
Compound (SMILES): COc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(C)C)CC2)c(=O)n4C)cn1
InChIKey: BZRKTLGOTQBGHQ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 3.48 nM (pChEMBL 8.460000038146973)
Descriptors: MW 432.53, ALogP 3.4, HBA 8, HBD 0, PSA 78.07, QED 0.49
Compound (SMILES): COc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)CN(C)C)CC2)c(=O)n4C)cn1
InChIKey: ABXIVYJPASFGEB-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 2.23 nM (pChEMBL 8.649999618530273)
Descriptors: MW 475.55, ALogP 2.08, HBA 9, HBD 0, PSA 98.38, QED 0.44
Compound (SMILES): COc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(CC(N)=O)CC2)c(=O)n4C)cn1
InChIKey: HXPCGVAFBABYDI-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 0.339 nM (pChEMBL 9.470000267028809)
Descriptors: MW 447.5, ALogP 1.48, HBA 9, HBD 1, PSA 121.16, QED 0.49
Compound (SMILES): COc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCOCC2)c(=O)n4C)cn1
InChIKey: CYLRJIMWCUJTBH-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 0.668 nM (pChEMBL 9.180000305175781)
Descriptors: MW 391.43, ALogP 2.71, HBA 8, HBD 0, PSA 84.06, QED 0.53
Compound (SMILES): Cn1c(=O)n(C2CCN(CC(F)(F)F)CC2)c2c3nc(-c4cnc5ccccc5c4)ccc3ncc21
InChIKey: KSWOHKLTWOQFCL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 20.5 nM (pChEMBL 7.690000057220459)
Descriptors: MW 492.51, ALogP 4.7, HBA 7, HBD 0, PSA 68.84, QED 0.37
Compound (SMILES): CNC(=O)N1CCC(n2c(=O)n(C)c3cnc4ccc(-c5ccc(OC)nc5)nc4c32)CC1
InChIKey: PMUAIGLZZYUTTE-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 1.15 nM (pChEMBL 8.9399995803833)
Descriptors: MW 447.5, ALogP 2.33, HBA 8, HBD 1, PSA 107.17, QED 0.52
Compound (SMILES): Cn1c(=O)n(C2CCN(C(=O)C(C)(C)O)CC2)c2c3nc(-c4cnc5ccccc5c4)ccc3ncc21
InChIKey: YPJJBVBXXWPJQT-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 0.568 nM (pChEMBL 9.25)
Descriptors: MW 496.57, ALogP 3.43, HBA 8, HBD 1, PSA 106.14, QED 0.41
Compound (SMILES): CN(C)CC(=O)N1CCC(n2c(=O)n(C)c3cnc4ccc(-c5ccc(N(C)C)nc5)nc4c32)CC1
InChIKey: NLOCQUUJIBXXNB-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 488.6, ALogP 2.14, HBA 9, HBD 0, PSA 92.39, QED 0.42
Compound (SMILES): Cn1c(=O)n(C2CCN(C(=O)C(C)(C)N)CC2)c2c3nc(-c4cnc5ccccc5c4)ccc3ncc21
InChIKey: JEWYIIZPXAXOBR-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 3.92 nM (pChEMBL 8.40999984741211)
Descriptors: MW 495.59, ALogP 3.4, HBA 8, HBD 1, PSA 111.93, QED 0.41
Compound (SMILES): Cn1c(=O)n([C@H]2CC[C@H](O)CC2)c2c3nc(-c4cnc5ccccc5c4)ccc3ncc21
InChIKey: LEDZNERMENQHCL-IYARVYRRSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 425.49, ALogP 3.97, HBA 7, HBD 1, PSA 85.83, QED 0.46
Compound (SMILES): Cn1c(=O)n([C@H]2CC[C@H](OCCO)CC2)c2c3nc(-c4cnc5ccccc5c4)ccc3ncc21
InChIKey: NXPKOOPSQRQLGO-MXVIHJGJSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 1.08 nM (pChEMBL 8.970000267028809)
Descriptors: MW 469.55, ALogP 3.99, HBA 8, HBD 1, PSA 95.06, QED 0.42
Compound (SMILES): COc1ncc(-c2ccc3ncc4c(c3n2)n([C@H]2CC[C@H](OCCO)CC2)c(=O)n4C)cn1
InChIKey: MTFFDZGRFRQITI-WKILWMFISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 2.09 nM (pChEMBL 8.680000305175781)
Descriptors: MW 450.5, ALogP 2.24, HBA 10, HBD 1, PSA 117.18, QED 0.48
Compound (SMILES): CN(C)c1ccc(-c2ccc3ncc4c(c3n2)n([C@H]2CC[C@H](OCCO)CC2)c(=O)n4C)cn1
InChIKey: ZZMGXCJDWSUNES-IYARVYRRSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 0.102 nM (pChEMBL 9.989999771118164)
Descriptors: MW 462.55, ALogP 2.9, HBA 9, HBD 1, PSA 98.3, QED 0.47
Compound (SMILES): CN(C)c1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(CC(F)(F)F)CC2)c(=O)n4C)cn1
InChIKey: WAMJHIPLMJJLBJ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 8.78 nM (pChEMBL 8.0600004196167)
Descriptors: MW 485.51, ALogP 3.61, HBA 8, HBD 0, PSA 72.08, QED 0.44
Compound (SMILES): Cn1cc(-c2ccc3ncc4c(c3n2)n(C2CCN(CC(F)(F)F)CC2)c(=O)n4C)cn1
InChIKey: OBRVVXHCETYKOV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 97.7 nM (pChEMBL 7.010000228881836)
Descriptors: MW 445.45, ALogP 2.88, HBA 8, HBD 0, PSA 73.77, QED 0.48
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n([C@H]2CC[C@H](OCCO)CC2)c(=O)n4C)cn1
InChIKey: LVEXSOMVMPNPIE-IYARVYRRSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 1.68 nM (pChEMBL 8.779999732971191)
Descriptors: MW 433.51, ALogP 3.15, HBA 8, HBD 1, PSA 95.06, QED 0.52
Compound (SMILES): COc1ncc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)[C@H](C)O)CC2)c(=O)n4C)cn1
InChIKey: DBDFQJQWQAVATL-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 2.59 nM (pChEMBL 8.59000015258789)
Descriptors: MW 463.5, ALogP 1.29, HBA 10, HBD 1, PSA 128.26, QED 0.48
Compound (SMILES): COc1ncc(-c2ccc3ncc4c(c3n2)n([C@H]2CC[C@H](C(N)=O)CC2)c(=O)n4C)cn1
InChIKey: JBLHXBPPTAVQLP-MQMHXKEQSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 433.47, ALogP 1.97, HBA 9, HBD 1, PSA 130.81, QED 0.52
Compound (SMILES): Cn1cc(-c2ccc3ncc4c(c3n2)n([C@H]2CC[C@H](C(N)=O)CC2)c(=O)n4C)cn1
InChIKey: SDJWQQUZGTZQLC-MQMHXKEQSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 23.3 nM (pChEMBL 7.630000114440918)
Descriptors: MW 405.46, ALogP 1.9, HBA 8, HBD 1, PSA 113.62, QED 0.56
Compound (SMILES): COCC(=O)N1CCC(n2c(=O)n(C)c3cnc4ccc(-c5cnc(OC)nc5)nc4c32)CC1
InChIKey: QDMLWRQDYNWDNC-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 4.97 nM (pChEMBL 8.300000190734863)
Descriptors: MW 463.5, ALogP 1.56, HBA 10, HBD 0, PSA 117.26, QED 0.44
Compound (SMILES): COc1ncc(-c2ccc3ncc4c(c3n2)n(C2CCN(CC(=O)N(C)C)CC2)c(=O)n4C)cn1
InChIKey: VMQKJOBTEJANRR-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 476.54, ALogP 1.47, HBA 10, HBD 0, PSA 111.27, QED 0.43
Compound (SMILES): Cn1c(=O)n([C@H]2CC[C@H](C(N)=O)CC2)c2c3nc(-c4cnn(CCO)c4)ccc3ncc21
InChIKey: HJEAAYNELPFMHP-CTYIDZIISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 16.2 nM (pChEMBL 7.789999961853027)
Descriptors: MW 435.49, ALogP 1.36, HBA 9, HBD 2, PSA 133.85, QED 0.49
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(c3ncccn3)CC2)c(=O)n4C)cn1
InChIKey: WVOHESNLMJHDRK-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 3.52 nM (pChEMBL 8.449999809265137)
Descriptors: MW 452.52, ALogP 3.29, HBA 9, HBD 0, PSA 94.62, QED 0.41
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(CCO)CC2)c(=O)n4C)cn1
InChIKey: DOBJOKJSJXZIOT-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 1.77 nM (pChEMBL 8.75)
Descriptors: MW 418.5, ALogP 2.28, HBA 8, HBD 1, PSA 89.07, QED 0.55
Compound (SMILES): Cn1c(=O)n([C@H]2CC[C@H](O)CC2)c2c3nc(-c4cn[nH]c4)ccc3ncc21
InChIKey: BYCVGFYVNZPDJW-JOCQHMNTSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 4.17 nM (pChEMBL 8.380000114440918)
Descriptors: MW 364.41, ALogP 2.15, HBA 7, HBD 2, PSA 101.62, QED 0.57
Compound (SMILES): COc1ncc(-c2ccc3ncc4c(c3n2)n([C@H]2CC[C@H](O)CC2)c(=O)n4C)cn1
InChIKey: MZGDSPJPVFTZAB-HDJSIYSDSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 0.974 nM (pChEMBL 9.010000228881836)
Descriptors: MW 406.45, ALogP 2.22, HBA 9, HBD 1, PSA 107.95, QED 0.56
Compound (SMILES): Cn1cc(-c2ccc3ncc4c(c3n2)n([C@H]2CC[C@H](O)CC2)c(=O)n4C)cn1
InChIKey: ZDEXVDRHVRCKFR-HDJSIYSDSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 7.44 nM (pChEMBL 8.130000114440918)
Descriptors: MW 378.44, ALogP 2.16, HBA 8, HBD 1, PSA 90.76, QED 0.58
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C)CC2)c(=O)n4C)cn1
InChIKey: XRLJNYCQTCOLHF-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 4.26 nM (pChEMBL 8.369999885559082)
Descriptors: MW 388.48, ALogP 2.92, HBA 7, HBD 0, PSA 68.84, QED 0.53
Compound (SMILES): Cn1c(=O)n([C@H]2CC[C@H](O)CC2)c2c3nc(-c4cc[nH]n4)ccc3ncc21
InChIKey: UGHUEKMXYXFWBE-HAQNSBGRSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 23.3 nM (pChEMBL 7.630000114440918)
Descriptors: MW 364.41, ALogP 2.15, HBA 7, HBD 2, PSA 101.62, QED 0.57
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(CC(N)=O)CC2)c(=O)n4C)cn1
InChIKey: YXFAAQVTSYIBFS-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 0.882 nM (pChEMBL 9.050000190734863)
Descriptors: MW 431.5, ALogP 1.78, HBA 8, HBD 1, PSA 111.93, QED 0.53
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)CN(C)C)CC2)c(=O)n4C)cn1
InChIKey: JFMAOEQGINOHKN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 4.09 nM (pChEMBL 8.390000343322754)
Descriptors: MW 459.55, ALogP 2.38, HBA 8, HBD 0, PSA 89.15, QED 0.47
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n([C@H]2CC[C@H](O)CC2)c(=O)n4C)cn1
InChIKey: LVIORTDEPFZDSH-WKILWMFISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 1.03 nM (pChEMBL 8.989999771118164)
Descriptors: MW 389.46, ALogP 3.13, HBA 7, HBD 1, PSA 85.83, QED 0.57