lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1cnc3[nH]ccc3c1)c(=O)n2CC1CCCO1
InChIKey: FTLUSDJTXDOWEA-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 376.42, ALogP 2.4, HBA 7, HBD 2, PSA 111.71, QED 0.57
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1cn[nH]c1)c(=O)n2C1CN(C(=O)OC(C)(C)C)C1
InChIKey: AOBVUGNSBXNKIU-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 397.44, ALogP 1.86, HBA 8, HBD 2, PSA 132.02, QED 0.67
Compound (SMILES): COc1ccc(-c2cc3c(C)nc(N)nc3n(C3CN(C(=O)OC(C)(C)C)C3)c2=O)cn1
InChIKey: AVUFBCPVZPCPIH-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 438.49, ALogP 2.54, HBA 9, HBD 1, PSA 125.46, QED 0.66
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1cnc3[nH]ccc3c1)c(=O)n2C1CN(C(=O)OC(C)(C)C)C1
InChIKey: VEWPVJKFGGHDSD-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 447.5, ALogP 3.02, HBA 8, HBD 2, PSA 132.02, QED 0.48
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1cncc(N)n1)c(=O)n2C1CCCC1
InChIKey: YMTCQIZKEYSDBK-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 337.39, ALogP 1.84, HBA 8, HBD 2, PSA 125.6, QED 0.73
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1cccc(Cl)n1)c(=O)n2C1CCCC1
InChIKey: ZXICMWVHOQEEBU-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 355.83, ALogP 3.51, HBA 6, HBD 1, PSA 86.69, QED 0.71
Compound (SMILES): CNc1nc(C)c2cc(-c3ccc(OC)nc3)c(=O)n(CCC3CC3)c2n1
InChIKey: JVZXYEXXWRTVHZ-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 365.44, ALogP 3.01, HBA 7, HBD 1, PSA 81.93, QED 0.72
Compound (SMILES): COc1ccc(-c2cc3c(C)nc(N)nc3n(CCC3CC3)c2=O)cn1
InChIKey: WHCDPTNSCYDFNC-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 351.41, ALogP 2.55, HBA 7, HBD 1, PSA 95.92, QED 0.76
Compound (SMILES): CNc1nc(C)c2cc(-c3cnn(C)c3)c(=O)n(C3CCCC3)c2n1
InChIKey: JYWKSRDSMVVVMC-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 338.42, ALogP 2.66, HBA 7, HBD 1, PSA 77.63, QED 0.79
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1cnn(C)c1)c(=O)n2C1CCCC1
InChIKey: UWVNMFMZWBKRHY-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 324.39, ALogP 2.2, HBA 7, HBD 1, PSA 91.62, QED 0.78
Compound (SMILES): CNc1nc(C)c2cc(-c3cnn(CC(F)F)c3)c(=O)n(C3CCCC3)c2n1
InChIKey: CKMMWYSNSBEFHH-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 388.42, ALogP 3.39, HBA 7, HBD 1, PSA 77.63, QED 0.72
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1cnn(CC(F)F)c1)c(=O)n2C1CCCC1
InChIKey: ICMGUSFUTMZWBU-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 374.39, ALogP 2.93, HBA 7, HBD 1, PSA 91.62, QED 0.76
Compound (SMILES): COc1ccc(-c2cc3c(C)nc(N)nc3n(CCN)c2=O)cn1
InChIKey: JRPMSPMSCBZJEK-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 326.36, ALogP 0.71, HBA 8, HBD 2, PSA 121.94, QED 0.72
Compound (SMILES): CNc1nc(C)c2cc(-c3ccc(OC)nc3)c(=O)n(CCN)c2n1
InChIKey: WXZLACDUBLZWMX-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 340.39, ALogP 1.17, HBA 8, HBD 2, PSA 107.95, QED 0.72
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1cnn(CC(C)(C)O)c1)c(=O)n2C1CCCC1
InChIKey: AMLADBZMQAZDAL-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 382.47, ALogP 2.43, HBA 8, HBD 2, PSA 111.85, QED 0.72
Compound (SMILES): COc1ccc(-c2cc3c(C)nc(N)nc3n(CC(C)C)c2=O)cn1
InChIKey: DYXQQYIVBKEQMC-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 339.4, ALogP 2.41, HBA 7, HBD 1, PSA 95.92, QED 0.78
Compound (SMILES): COc1ccc(-c2cc3c(C)nc(N)nc3n(CC3CCOCC3)c2=O)cn1
InChIKey: YJIXSCDOMBFTQX-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 381.44, ALogP 2.18, HBA 8, HBD 1, PSA 105.15, QED 0.74
Compound (SMILES): COc1ccc(-c2cc3c(C)nc(N)nc3n(CC3(F)CCOCC3)c2=O)cn1
InChIKey: MFBJHDCFUUVEIB-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 399.43, ALogP 2.27, HBA 8, HBD 1, PSA 105.15, QED 0.72
Compound (SMILES): COc1ccc(-c2cc3c(C)nc(N)nc3n(CC(C)(C)F)c2=O)cn1
InChIKey: AFDAULPSKXLCAX-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 357.39, ALogP 2.5, HBA 7, HBD 1, PSA 95.92, QED 0.77
Compound (SMILES): CNc1nc(C)c2cc(-c3c[nH]c(C)n3)c(=O)n(C3CCCC3)c2n1
InChIKey: VTHXLMGKYXMDRD-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 338.42, ALogP 2.96, HBA 6, HBD 2, PSA 88.49, QED 0.77
Compound (SMILES): COc1ccc(-c2cc3c(C)nc(N)nc3n(C3CCN(C(=O)OC(C)(C)C)C3)c2=O)cn1
InChIKey: VRBVFUKBFVVTPZ-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 452.52, ALogP 2.93, HBA 9, HBD 1, PSA 125.46, QED 0.64
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1ccc(N3CCCC3)nc1)c(=O)n2[C@H]1CC[C@H](O)CC1
InChIKey: AHQRMXFHEMSOSW-QAQDUYKDSA-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 420.52, ALogP 2.82, HBA 8, HBD 2, PSA 110.16, QED 0.67
Compound (SMILES): COc1ncc(-c2cc3c(C)nc(N)nc3n(C3CCCC3)c2=O)cc1F
InChIKey: HTSCRPWAPBUQNJ-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 369.4, ALogP 3.01, HBA 7, HBD 1, PSA 95.92, QED 0.76
Compound (SMILES): COc1ncc(-c2cc3c(C)nc(N)nc3n(C3CCCC3)c2=O)cn1
InChIKey: HNEJUXXHBRXUKZ-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 352.4, ALogP 2.26, HBA 8, HBD 1, PSA 108.81, QED 0.77
Compound (SMILES): CCc1cccc(-c2cc3c(C)nc(N)nc3n(C3CCCC3)c2=O)c1
InChIKey: BPORGSIWKJAQQV-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 348.45, ALogP 4.03, HBA 5, HBD 1, PSA 73.8, QED 0.78
Compound (SMILES): Cc1cc(-c2cc3c(C)nc(N)nc3n(C3CCCC3)c2=O)cnc1N(C)C
InChIKey: GOFSIDFUVFJQQS-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 378.48, ALogP 3.23, HBA 7, HBD 1, PSA 89.93, QED 0.75
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1ccc(N3CCCC3)nc1)c(=O)n2C1CCCC1
InChIKey: AFERABYICQULFL-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 390.49, ALogP 3.46, HBA 7, HBD 1, PSA 89.93, QED 0.74
Compound (SMILES): COc1ncc(-c2cc3c(C)nc(N)nc3n(C3CCOCC3)c2=O)cn1
InChIKey: TZMOTMMMNIITML-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 368.4, ALogP 1.5, HBA 9, HBD 1, PSA 118.04, QED 0.74
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1cccc(CO)c1)c(=O)n2C1CCOCC1
InChIKey: RZOVMADNRJFLDO-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 366.42, ALogP 2.19, HBA 7, HBD 2, PSA 103.26, QED 0.74
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1ccc3c(c1)OCCO3)c(=O)n2[C@H]1CC[C@H](O)CC1
InChIKey: JWSHRTLBVPHIIM-SHTZXODSSA-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 408.46, ALogP 2.6, HBA 8, HBD 2, PSA 112.49, QED 0.67
Compound (SMILES): COc1ccc(-c2cc3c(C)nc(N)nc3n(C3CCCC3)c2=O)cc1F
InChIKey: WAWYTTSOMZIFNS-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 368.41, ALogP 3.61, HBA 6, HBD 1, PSA 83.03, QED 0.76
Compound (SMILES): COc1ncc(-c2cc3c(C)nc(N)nc3n(C3CCOCC3)c2=O)cc1F
InChIKey: JMQRVKSTNHIKTJ-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 1.43 nM (pChEMBL 8.850000381469727)
Descriptors: MW 385.4, ALogP 2.24, HBA 8, HBD 1, PSA 105.15, QED 0.74
Compound (SMILES): COc1ncc(-c2cc3c(C)nc(N)nc3n(C(C)C)c2=O)cn1
InChIKey: MCNONSMQRZNVDL-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 326.36, ALogP 1.73, HBA 8, HBD 1, PSA 108.81, QED 0.78
Compound (SMILES): Cc1nc(N)nc2c1cc(-c1cnc(=O)[nH]c1)c(=O)n2C(C)C
InChIKey: MASZVOUWNBDWFU-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-Kα using an in vitro kinase assay. PI3-Kα 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-Kα reaction resulting in a decrease in FP signal.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 312.33, ALogP 1.01, HBA 7, HBD 2, PSA 119.55, QED 0.73
Compound (SMILES): COc1ccnc(N2CC3CN(C(=O)c4cccc5ccccc45)CC3C2)n1
InChIKey: GBOGADFPCXULPQ-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Receptor Radioligand Binding Assay: Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1× Pen/Strep, 600 μg/mL G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 10 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and vortexed for 45 sec prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-SB674042 (Moravek Corporation, specific activity=35.3 Ci/mmol), diluted to a 10 nM concentration in PBS (4 nM final). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentrations (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM (1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea, CAS Registry #288150-92-5). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-5B674042 diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 227 nM (pChEMBL 6.639999866485596)
Descriptors: MW 374.44, ALogP 2.85, HBA 5, HBD 0, PSA 58.56, QED 0.71
Compound (SMILES): CCOc1ccccc1C(=O)N1CC2CN(c3nccc(OC)n3)CC2C1
InChIKey: KNSQXGQTBLTKPU-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 8999 nM (pChEMBL 5.050000190734863)
Descriptors: MW 368.44, ALogP 2.09, HBA 6, HBD 0, PSA 67.79, QED 0.81
Compound (SMILES): COc1ccnc(N2CC3CN(C(=O)c4c(OC)ccc5ccccc45)CC3C2)n1
InChIKey: PWRHYDCPWHULKG-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Receptor Radioligand Binding Assay: Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1× Pen/Strep, 600 μg/mL G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 10 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and vortexed for 45 sec prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-SB674042 (Moravek Corporation, specific activity=35.3 Ci/mmol), diluted to a 10 nM concentration in PBS (4 nM final). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentrations (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM (1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea, CAS Registry #288150-92-5). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-5B674042 diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 173 nM (pChEMBL 6.760000228881836)
Descriptors: MW 404.47, ALogP 2.86, HBA 6, HBD 0, PSA 67.79, QED 0.67
Compound (SMILES): O=C(c1ccccc1-c1ccccc1)N1CC2CN(c3nccc(-c4cn[nH]c4)n3)CC2C1
InChIKey: DHUXGFAIUQGLHZ-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 2272 nM (pChEMBL 5.639999866485596)
Descriptors: MW 436.52, ALogP 3.74, HBA 5, HBD 1, PSA 78.01, QED 0.53
Compound (SMILES): O=C(c1ccccc1-c1cccs1)N1CC2CN(c3nccc(-c4cn[nH]c4)n3)CC2C1
InChIKey: MIEKLHFLBFABFC-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 689 nM (pChEMBL 6.159999847412109)
Descriptors: MW 442.55, ALogP 3.8, HBA 6, HBD 1, PSA 78.01, QED 0.52
Compound (SMILES): Cc1cnc(C)c(N2CC3CN(C(=O)c4ccccc4-c4cccs4)CC3C2)n1
InChIKey: DKVIZUUTLAGTIC-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Receptor Radioligand Binding Assay: Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1× Pen/Strep, 600 μg/mL G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 10 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and vortexed for 45 sec prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-SB674042 (Moravek Corporation, specific activity=35.3 Ci/mmol), diluted to a 10 nM concentration in PBS (4 nM final). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentrations (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM (1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea, CAS Registry #288150-92-5). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-5B674042 diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 404.54, ALogP 4.03, HBA 5, HBD 0, PSA 49.33, QED 0.66
Compound (SMILES): Cc1cnc(N2CC3CN(C(=O)c4ccccc4-c4ccccc4)CC3C2)c(C)n1
InChIKey: WURCDDFLPQEWFC-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 579 nM (pChEMBL 6.239999771118164)
Descriptors: MW 398.51, ALogP 3.97, HBA 4, HBD 0, PSA 49.33, QED 0.67
Compound (SMILES): Cc1nc2ccccc2nc1N1CC2CN(C(=O)c3ccccc3-c3cccs3)CC2C1
InChIKey: DXISUHVJHZZFSX-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 207 nM (pChEMBL 6.679999828338623)
Descriptors: MW 440.57, ALogP 4.88, HBA 5, HBD 0, PSA 49.33, QED 0.46
Compound (SMILES): Cc1nc2ccccc2nc1N1CC2CN(C(=O)c3ccccc3-c3ccccc3)CC2C1
InChIKey: AUOVDLRSGKHWLH-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 415 nM (pChEMBL 6.380000114440918)
Descriptors: MW 434.54, ALogP 4.81, HBA 4, HBD 0, PSA 49.33, QED 0.46
Compound (SMILES): Cc1cc(C)nc(N2CC3CN(C(=O)c4ccccc4-n4cccn4)CC3C2)n1
InChIKey: RHNDWDDUZXTNJU-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Biological Assay: The in vitro affinity of the compounds for the human orexin-1 and orexin-2 receptors was determined by competitive radioligand binding using [3H]SB SB674042 (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Langmead et al., British Journal of Pharmacology 2004, 141:340-346) and [3H]EMPA (N-ethyl-2[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl acetamide) (Malherbe et al., British Journal of Pharmacology, 2009, 156(8), 1326-1341), respectively. The in vitro functional antagonism of the compounds on the human orexin-1 and orexin-2 receptors was determined using fluorometric imaging plate reader (FLIPR) based calcium assays.
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 388.48, ALogP 2.49, HBA 6, HBD 0, PSA 67.15, QED 0.69
Compound (SMILES): COc1cc(OC)nc(N2CC3CN(C(=O)c4c(F)cccc4-c4ncccn4)CC3C2)n1
InChIKey: MVBAVBLSBRYPRO-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Receptor Radioligand Binding Assay: Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1× Pen/Strep, 600 μg/mL G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 10 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and vortexed for 45 sec prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-SB674042 (Moravek Corporation, specific activity=35.3 Ci/mmol), diluted to a 10 nM concentration in PBS (4 nM final). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentrations (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM (1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea, CAS Registry #288150-92-5). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-5B674042 diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 450.47, ALogP 2.3, HBA 8, HBD 0, PSA 93.57, QED 0.58