lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3C23CCCC(CCC2)C3)c1=O
InChIKey: HQRWWKRMPLZJMJ-YHSYXWOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 5345 nM (pChEMBL 5.269999980926514)
Descriptors: MW 435.57, ALogP 4.77, HBA 5, HBD 1, PSA 75.43, QED 0.75
Compound (SMILES): C[C@@H]1C[C@@H]2C[C@H](C1)C[C@@H](N1[C@@H]3CCC[C@H]1C[C@@H](n1c(=O)c(C(=O)O)nc4ccccc41)C3)C2
InChIKey: OWAGGONYNCKXDC-PCXLCNFCSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 75.4 nM (pChEMBL 7.119999885559082)
Descriptors: MW 449.6, ALogP 4.87, HBA 5, HBD 1, PSA 75.43, QED 0.72
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCCCCCC2)c1=O
InChIKey: DNQQJKRDKSYDKP-JKHIJQBDSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: ORL-1 Receptor Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1 nM [3H]-nociceptin (NEN; 87.7 Ci/mmole) with 10-20 μg membrane protein in a final volume of 500 μL binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10 nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25° C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 5004 ice-cold binding buffer. Filter plates were subsequently dried at 50° C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 18180 nM (pChEMBL 4.739999771118164)
Descriptors: MW 465.64, ALogP 5.94, HBA 5, HBD 1, PSA 75.43, QED 0.61
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: XYFPWWZEPKGCCK-SFHVURJKSA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: Inhibition of LYN (unknown origin) by FRET assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47
Compound (SMILES): C=CC(=O)N[C@H]1CC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: SSDFTYWIYVWCIE-KDURUIRLSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 909.9 nM (pChEMBL 6.039999961853027)
Descriptors: MW 454.53, ALogP 4.65, HBA 7, HBD 2, PSA 107.95, QED 0.41
Compound (SMILES): CN(C)C/C=C/C(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: IDIZKFVKMFGLPN-FTUXVVSKSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 48.8 nM (pChEMBL 7.309999942779541)
Descriptors: MW 497.6, ALogP 4.15, HBA 8, HBD 1, PSA 102.4, QED 0.38
Compound (SMILES): C=CC(=O)N1CCC(n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: KALPRSFUZYGTNU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47
Compound (SMILES): c1ccc(CN2C3CCC2CC(Nc2ccc4[nH]ncc4c2)C3)cc1
InChIKey: RTCFKJVSDGLJAM-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Inhibition Assay: Inhibition of Rho kinase 2 and Rho kinase 1 activity was determined using the IMAP™ Screening Express Kit (Molecular Devices product number #8073). Rho kinase 2 enzyme (Upstate/Chemicon #14-451), Rho kinase 1 (Upstate/Chemicon #14-601) and Flourescein tagged substrate peptide F1-AKRRRLSSLRA (Molecular Devices product number R7184) was pre-incubated with a test compound for 5 minutes in buffer containing 10 mM Tris-HCl pH 7.2, 10 mM MgCl2, and 0.1% BSA. Following the pre-incubation, 10 μM ATP was added to initiate the reaction. After 60 minutes at room temperature, Molecular Devices IMAP™ binding solution was added to bind phosphorylated substrate. After 30 minutes of incubation in the presence of the IMAP™ beads, the fluorescence polarization was read and the ratio was reported as mP.
Measurement: Ki = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 332.45, ALogP 4.17, HBA 3, HBD 2, PSA 43.95, QED 0.75
Compound (SMILES): Cc1ccc(CN2C3CCC2CC(Nc2ccc4[nH]ncc4c2)C3)cc1
InChIKey: CUJPUWSIKWTBRS-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Inhibition Assay: Inhibition of Rho kinase 2 and Rho kinase 1 activity was determined using the IMAP™ Screening Express Kit (Molecular Devices product number #8073). Rho kinase 2 enzyme (Upstate/Chemicon #14-451), Rho kinase 1 (Upstate/Chemicon #14-601) and Flourescein tagged substrate peptide F1-AKRRRLSSLRA (Molecular Devices product number R7184) was pre-incubated with a test compound for 5 minutes in buffer containing 10 mM Tris-HCl pH 7.2, 10 mM MgCl2, and 0.1% BSA. Following the pre-incubation, 10 μM ATP was added to initiate the reaction. After 60 minutes at room temperature, Molecular Devices IMAP™ binding solution was added to bind phosphorylated substrate. After 30 minutes of incubation in the presence of the IMAP™ beads, the fluorescence polarization was read and the ratio was reported as mP.
Measurement: Ki = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 346.48, ALogP 4.48, HBA 3, HBD 2, PSA 43.95, QED 0.73
Compound (SMILES): OCCOc1cccc(CN2C3CCC2CC(Nc2ccc4[nH]ncc4c2)C3)c1
InChIKey: HWGXVQXOZZVGKP-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Inhibition Assay: Inhibition of Rho kinase 2 and Rho kinase 1 activity was determined using the IMAP™ Screening Express Kit (Molecular Devices product number #8073). Rho kinase 2 enzyme (Upstate/Chemicon #14-451), Rho kinase 1 (Upstate/Chemicon #14-601) and Flourescein tagged substrate peptide F1-AKRRRLSSLRA (Molecular Devices product number R7184) was pre-incubated with a test compound for 5 minutes in buffer containing 10 mM Tris-HCl pH 7.2, 10 mM MgCl2, and 0.1% BSA. Following the pre-incubation, 10 μM ATP was added to initiate the reaction. After 60 minutes at room temperature, Molecular Devices IMAP™ binding solution was added to bind phosphorylated substrate. After 30 minutes of incubation in the presence of the IMAP™ beads, the fluorescence polarization was read and the ratio was reported as mP.
Measurement: Ki = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 392.5, ALogP 3.54, HBA 5, HBD 3, PSA 73.41, QED 0.57
Compound (SMILES): Cc1ccc(CN2C3CCC2CC(Nc2ccc4[nH]ncc4c2)C3)cc1OCCO
InChIKey: ODUYVHAFJTXMAF-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Inhibition Assay: Inhibition of Rho kinase 2 and Rho kinase 1 activity was determined using the IMAP™ Screening Express Kit (Molecular Devices product number #8073). Rho kinase 2 enzyme (Upstate/Chemicon #14-451), Rho kinase 1 (Upstate/Chemicon #14-601) and Flourescein tagged substrate peptide F1-AKRRRLSSLRA (Molecular Devices product number R7184) was pre-incubated with a test compound for 5 minutes in buffer containing 10 mM Tris-HCl pH 7.2, 10 mM MgCl2, and 0.1% BSA. Following the pre-incubation, 10 μM ATP was added to initiate the reaction. After 60 minutes at room temperature, Molecular Devices IMAP™ binding solution was added to bind phosphorylated substrate. After 30 minutes of incubation in the presence of the IMAP™ beads, the fluorescence polarization was read and the ratio was reported as mP.
Measurement: Ki = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 406.53, ALogP 3.85, HBA 5, HBD 3, PSA 73.41, QED 0.56
Compound (SMILES): N=C(N)c1ccc(CNC(=O)CNC(=O)[C@@H](CO)NS(=O)(=O)Cc2cccc(C(=O)O)c2)cc1
InChIKey: FVQTZAVABYIQGN-QGZVFWFLSA-N
Target: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 720 nM (pChEMBL 6.139999866485596)
Descriptors: MW 491.53, ALogP -1.12, HBA 7, HBD 7, PSA 211.77, QED 0.14
Compound (SMILES): COC(=O)c1ccc(CS(=O)(=O)N[C@H](CO)C(=O)NCC(=O)NCc2ccc(C(=N)N)cc2)cc1
InChIKey: VNHHRJRZJZNYCL-GOSISDBHSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 505.55, ALogP -1.03, HBA 8, HBD 6, PSA 200.77, QED 0.12
Compound (SMILES): N=C(N)c1ccc(CNC(=O)CNC(=O)[C@@H](CO)NS(=O)(=O)Cc2ccc(C(=O)O)cc2)cc1
InChIKey: SWRWEBCZNDCUHE-QGZVFWFLSA-N
Target: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 491.53, ALogP -1.12, HBA 7, HBD 7, PSA 211.77, QED 0.14
Compound (SMILES): COC(=O)c1ccccc1CS(=O)(=O)N[C@H](CO)C(=O)NCC(=O)NCc1ccc(C(=N)N)cc1
InChIKey: CFTOBJMSXPABSM-GOSISDBHSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 505.55, ALogP -1.03, HBA 8, HBD 6, PSA 200.77, QED 0.12
Compound (SMILES): N=C(N)c1ccc(CNC(=O)CNC(=O)[C@@H](CO)NS(=O)(=O)Cc2ccccc2C(=O)O)cc1
InChIKey: IYWSRHAQECQVEQ-QGZVFWFLSA-N
Target: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 491.53, ALogP -1.12, HBA 7, HBD 7, PSA 211.77, QED 0.14
Compound (SMILES): C[C@H](NC(=O)[C@@H](CO)NS(=O)(=O)Cc1ccc(C(=O)O)cc1)C(=O)NCc1ccc(C(=N)N)cc1
InChIKey: PTHXQAIWUFJVSU-SCLBCKFNSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 505.55, ALogP -0.73, HBA 7, HBD 7, PSA 211.77, QED 0.14
Compound (SMILES): C[C@H](NC(=O)[C@@H](CO)NS(=O)(=O)Cc1cccc(C(=O)O)c1)C(=O)NCc1ccc(C(=N)N)cc1
InChIKey: BBAZXQQFVDXNHA-SCLBCKFNSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 505.55, ALogP -0.73, HBA 7, HBD 7, PSA 211.77, QED 0.14
Compound (SMILES): C[C@H](NC(=O)[C@@H](CO)NS(=O)(=O)Cc1ccc(C#N)cc1)C(=O)NCc1ccc(C(=N)N)cc1
InChIKey: UMTXMVBYSMIVTH-IFXJQAMLSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 8500 nM (pChEMBL 5.070000171661377)
Descriptors: MW 486.55, ALogP -0.56, HBA 7, HBD 6, PSA 198.26, QED 0.18
Compound (SMILES): N=C(N)c1ccc(CNC(=O)CNC(=O)[C@@H](CO)NS(=O)(=O)Cc2ccc(CN)cc2)cc1
InChIKey: XTINWPDNJKDTDS-GOSISDBHSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 476.56, ALogP -1.36, HBA 7, HBD 7, PSA 200.49, QED 0.14
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@H](CN)NC(=O)[C@@H](CO)NS(=O)(=O)Cc2ccccc2)cc1
InChIKey: BZFNGVIFENBIEV-ZWKOTPCHSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 476.56, ALogP -1.49, HBA 7, HBD 7, PSA 200.49, QED 0.14
Compound (SMILES): CC(O)[C@H](NC(=O)[C@@H](CO)NS(=O)(=O)Cc1ccccc1)C(=O)NCc1ccc(C(=N)N)cc1
InChIKey: YUESBYLBLODZCY-BRQZFJGMSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 491.57, ALogP -1.07, HBA 7, HBD 7, PSA 194.7, QED 0.14
Compound (SMILES): CC(OCc1ccccc1)[C@H](NC(=O)[C@@H](CO)NS(=O)(=O)Cc1ccccc1)C(=O)NCc1ccc(C(=N)N)cc1
InChIKey: JXDRVTULOVVFJK-KDVIAZGZSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 581.7, ALogP 1.16, HBA 7, HBD 6, PSA 183.7, QED 0.11
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@H](CO)NC(=O)[C@@H](CO)NS(=O)(=O)Cc2cccc(C(=O)O)c2)cc1
InChIKey: BFBUYZVPTHCXCJ-ZWKOTPCHSA-N
Target: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 521.55, ALogP -1.76, HBA 8, HBD 8, PSA 232, QED 0.11
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@H](CO)NC(=O)[C@@H](CO)NS(=O)(=O)Cc2ccc(C(=O)O)cc2)cc1
InChIKey: ZUGQWKKBKUBIAV-ZWKOTPCHSA-N
Target: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 521.55, ALogP -1.76, HBA 8, HBD 8, PSA 232, QED 0.11
Compound (SMILES): COC(=O)c1ccc(CS(=O)(=O)N[C@H](CO)C(=O)N[C@@H](CO)C(=O)NCc2ccc(C(=N)N)cc2)cc1
InChIKey: ZMSQIVBNHIMPNU-RBUKOAKNSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 535.58, ALogP -1.67, HBA 9, HBD 7, PSA 221, QED 0.09
Compound (SMILES): N=C(N)c1ccc(CNC(=O)CNC(=O)[C@@H](CO)NS(=O)(=O)Cc2ccc(Cl)cc2)cc1
InChIKey: SJXWFXDEIBMMEG-QGZVFWFLSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 7900 nM (pChEMBL 5.099999904632568)
Descriptors: MW 481.96, ALogP -0.16, HBA 6, HBD 6, PSA 174.47, QED 0.19
Compound (SMILES): Cc1ccc(CS(=O)(=O)N[C@H](CO)C(=O)NCC(=O)NCc2ccc(C(=N)N)cc2)cc1
InChIKey: CYBWAZVYPDOAOW-GOSISDBHSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 461.54, ALogP -0.51, HBA 6, HBD 6, PSA 174.47, QED 0.19
Compound (SMILES): N=C(N)c1ccc(CNC(=O)CNC(=O)[C@@H](CO)NS(=O)(=O)Cc2ccc(F)cc2)cc1
InChIKey: PLWLISMFLWIBNF-QGZVFWFLSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 7900 nM (pChEMBL 5.099999904632568)
Descriptors: MW 465.51, ALogP -0.68, HBA 6, HBD 6, PSA 174.47, QED 0.19
Compound (SMILES): N=C(N)c1ccc(CNC(=O)CNC(=O)[C@@H](CO)NS(=O)(=O)Cc2ccc(Cl)c(Cl)c2)cc1
InChIKey: ITGOAPKQQWGASV-QGZVFWFLSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 516.41, ALogP 0.49, HBA 6, HBD 6, PSA 174.47, QED 0.19
Compound (SMILES): N=C(N)c1ccc(CNC(=O)CNC(=O)[C@@H](CO)NS(=O)(=O)Cc2ccncc2)cc1
InChIKey: IBTFWKISFQNFGQ-MRXNPFEDSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 448.51, ALogP -1.42, HBA 7, HBD 6, PSA 187.36, QED 0.18
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](CO)NS(=O)(=O)Cc2ccccc2)cc1
InChIKey: JRGYHLAOYQDMNM-LEWJYISDSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 518.64, ALogP -0.32, HBA 7, HBD 7, PSA 200.49, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@H](CCCCNC(=O)COCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCN)NC(=O)[C@@H](CO)NS(=O)(=O)Cc2ccccc2)cc1
InChIKey: WWDFPEZFNGBGEX-ZESVVUHVSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 985.17, ALogP -1.95, HBA 17, HBD 9, PSA 332.53, QED 0.02
Compound (SMILES): N=C(N)c1ccc(CNC(=O)CNC(=O)C(N)CNS(=O)(=O)Cc2ccccc2)cc1
InChIKey: GQVFTAXOXBLSOQ-UHFFFAOYSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 446.53, ALogP -0.85, HBA 6, HBD 6, PSA 180.26, QED 0.19
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CO)NS(=O)(=O)Cc2ccccc2)cc1
InChIKey: LEHTWFAAQZWNNG-SFTDATJTSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 8500 nM (pChEMBL 5.070000171661377)
Descriptors: MW 527.61, ALogP -0.48, HBA 7, HBD 7, PSA 203.15, QED 0.11
Compound (SMILES): N=C(N)c1ccc(CNC(=O)CNC(=O)[C@H](CO)NS(=O)(=O)Cc2ccc(CC(=O)O)cc2)cc1
InChIKey: MVESHNBSRMOFED-SFHVURJKSA-N
Target: Prothrombin (SINGLE PROTEIN), Rattus norvegicus
UniProt: P18292
Assay: Enzyme Assay: Inhibition constant of the compound against Thrombin
Measurement: Ki = 60000 nM (pChEMBL 4.21999979019165)
Descriptors: MW 505.55, ALogP -1.19, HBA 7, HBD 7, PSA 211.77, QED 0.13
Compound (SMILES): O=S(=O)(NCCOc1ccc2c(c1)C(C1(c3ccc(Cl)cc3)CCC1)NCC2)C1CCNC1
InChIKey: RYAARGWQEZMYTP-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent glycine transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48067
Assay: Radioligand Binding Assay: Radioligand binding to human GlyT1c transporter-expressing membranes was carried out as described in Mezler et al., Molecular Pharmacology 74:1705-1715, 2008.More specifically, [3H]-(R)-NPTS radioligand binding to human GlyT1c transporter-expressing membranes was measured in duplicate in a total volume of 200 ul in 96-well plates. To 100 ul of membrane suspension (yielding a final membrane protein concentration of 50 ug/ml) in assay buffer (120 mM NaCl, 2 mM KCl, 10 mM Hepes, 1 mM MgCl2, 1 mM CaCl2, pH 7.5) 80 ul of [3H]-(R)-NPTS (0.5 nM final) were added in assay buffer. For competition experiments 10 ul of buffer or unlabeled compound solution obtained from dilution series of test compounds in DMSO followed. An intermediate 1:10 dilution in assay buffer yielded a final DMSO concentration of 1%. Non-specific binding was determined in the presence of 10 uM Org24598 (or its racemate Org24461) for [3H]-(R)-NPTS.
Measurement: Ki < 10000 nM (pChEMBL 5)
Descriptors: MW 490.07, ALogP 3.31, HBA 5, HBD 3, PSA 79.46, QED 0.5
Compound (SMILES): CC(C)(C)OC(=O)c1ccc(-n2[nH]cc(-n3ccnn3)c2=O)nc1
InChIKey: HWQQDVNGHZIALS-UHFFFAOYSA-N
Target: Hypoxia-inducible factor 1-alpha inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWT6
Assay: Inhibition of recombinant human FIH using 2OG as substrate and Fe2 as co-factor assessed as hydroxylation incubated for 15 mins in presence of L-ascorbate by LC-MS analysis
Measurement: IC50 = 66000 nM (pChEMBL 4.179999828338623)
Descriptors: MW 328.33, ALogP 1.1, HBA 8, HBD 1, PSA 107.69, QED 0.72
Compound (SMILES): O=c1c(-n2ccnn2)c[nH]n1-c1cc(N2CCOCC2)ncn1
InChIKey: IJMBOKOTALXLKS-UHFFFAOYSA-N
Target: Prolyl 3-hydroxylase OGFOD1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N543
Assay: Inhibition of recombinant human OGFOD1 using 2OG as substrate and Fe2 as co-factor assessed as hydroxylation incubated for 15 mins in presence of L-ascorbate by MALDI-TOF MS analysis
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 314.31, ALogP -0.63, HBA 9, HBD 1, PSA 106.75, QED 0.69
Compound (SMILES): COc1cc(N2CC3CN(C(=O)c4c(F)cccc4-n4nccn4)CC3C2)nc(N(C)C)n1
InChIKey: BKAVUKDORGWRAO-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 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 452.49, ALogP 1.48, HBA 9, HBD 0, PSA 92.51, QED 0.57
Compound (SMILES): CN(C)c1cc(N2CC3CN(C(=O)c4ccccc4-n4nccn4)CC3C2)nc(C(F)(F)F)n1
InChIKey: OMGMLXZAIWEESM-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 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 472.48, ALogP 2.35, HBA 8, HBD 0, PSA 83.28, QED 0.58
Compound (SMILES): CN(C)c1cc(N2CC3CN(C(=O)c4c(F)cccc4-n4nccn4)CC3C2)nc(C(F)(F)F)n1
InChIKey: USSWCJBLIIGXQA-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Receptor Radioligand Binding Assay: HEK293 stably expressing human orexin-2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), in DMEM, 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 1×HEPES, 600 ug/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 just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moravek Corporation, specific activity=27 Ci/mmol), diluted to a 20 nM concentration in PBS (5 nM final concentration). 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 (N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylnaphthalene-1-carboxamide, CAS Registry #1089563-88-1). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA 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 = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 490.47, ALogP 2.49, HBA 8, HBD 0, PSA 83.28, QED 0.52
Compound (SMILES): COc1cc(N2CC3CN(C(=O)c4cc(F)ccc4-n4nccn4)CC3C2)nc(N(C)C)n1
InChIKey: DOPCTFLLQXBISR-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Receptor Radioligand Binding Assay: HEK293 stably expressing human orexin-2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), in DMEM, 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 1×HEPES, 600 ug/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 just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moravek Corporation, specific activity=27 Ci/mmol), diluted to a 20 nM concentration in PBS (5 nM final concentration). 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 (N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylnaphthalene-1-carboxamide, CAS Registry #1089563-88-1). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA 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 = 447 nM (pChEMBL 6.349999904632568)
Descriptors: MW 452.49, ALogP 1.48, HBA 9, HBD 0, PSA 92.51, QED 0.57
Compound (SMILES): COc1cc(N2CC3CN(C(=O)c4ccccc4-n4nccn4)CC3C2)nc(N(C)C)n1
InChIKey: JCZKDUWJCWYWSC-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 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 434.5, ALogP 1.34, HBA 9, HBD 0, PSA 92.51, QED 0.59
Compound (SMILES): CN(C)c1cc(N2CC3CN(C(=O)c4ccc(F)cc4-n4nccn4)CC3C2)nc(C(F)(F)F)n1
InChIKey: UQVBWHBTBGUFNT-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 = 154 nM (pChEMBL 6.809999942779541)
Descriptors: MW 490.47, ALogP 2.49, HBA 8, HBD 0, PSA 83.28, QED 0.52
Compound (SMILES): COc1cc(N2CC3CN(C(=O)c4ccc(F)cc4-n4nccn4)CC3C2)nc(N(C)C)n1
InChIKey: VBWSYPVWXJCAFJ-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 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 452.49, ALogP 1.48, HBA 9, HBD 0, PSA 92.51, QED 0.57
Compound (SMILES): Cc1cc(C)nc(N2CC3CN(C(=O)c4sccc4-n4cccc4)CC3C2)n1
InChIKey: DVFNTCCOGHJMNT-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 393.52, ALogP 3.15, HBA 6, HBD 0, PSA 54.26, QED 0.69
Compound (SMILES): CN(C)c1cc(N2CC3CN(C(=O)c4cc(F)ccc4-n4nccn4)CC3C2)nc(C(F)(F)F)n1
InChIKey: IIGOHRICMDAQQK-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Receptor Radioligand Binding Assay: HEK293 stably expressing human orexin-2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), in DMEM, 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 1×HEPES, 600 ug/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 just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moravek Corporation, specific activity=27 Ci/mmol), diluted to a 20 nM concentration in PBS (5 nM final concentration). 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 (N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylnaphthalene-1-carboxamide, CAS Registry #1089563-88-1). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA 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 = 691 nM (pChEMBL 6.159999847412109)
Descriptors: MW 490.47, ALogP 2.49, HBA 8, HBD 0, PSA 83.28, QED 0.52
Compound (SMILES): Cc1cc(C)nc(N2CC3CN(C(=O)c4ccnn4-c4ccccc4)CC3C2)n1
InChIKey: VIHDZDWPQOPCLB-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Receptor Radioligand Binding Assay: HEK293 stably expressing human orexin-2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), in DMEM, 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 1×HEPES, 600 ug/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 just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moravek Corporation, specific activity=27 Ci/mmol), diluted to a 20 nM concentration in PBS (5 nM final concentration). 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 (N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylnaphthalene-1-carboxamide, CAS Registry #1089563-88-1). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA 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 = 6708 nM (pChEMBL 5.170000076293945)
Descriptors: MW 388.48, ALogP 2.49, HBA 6, HBD 0, PSA 67.15, QED 0.69
Compound (SMILES): Cc1cc(C)nc(N2CC3CN(C(=O)c4cccc5cccnc45)CC3C2)n1
InChIKey: YJTCYUPZJYYZLO-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 373.46, ALogP 2.85, HBA 5, HBD 0, PSA 62.22, QED 0.69
Compound (SMILES): Cc1cc(C)nc(N2CC3CN(C(=O)c4sccc4-c4ccccc4)CC3C2)n1
InChIKey: BVINMOXFXQBPAM-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 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 404.54, ALogP 4.03, HBA 5, HBD 0, PSA 49.33, QED 0.66
Compound (SMILES): Cc1cc(C)nc(N2CC3CN(C(=O)c4occc4-c4ccccc4)CC3C2)n1
InChIKey: QASJCXBBWDFBRS-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Receptor Radioligand Binding Assay: HEK293 stably expressing human orexin-2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), in DMEM, 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 1×HEPES, 600 ug/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 just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moravek Corporation, specific activity=27 Ci/mmol), diluted to a 20 nM concentration in PBS (5 nM final concentration). 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 (N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylnaphthalene-1-carboxamide, CAS Registry #1089563-88-1). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA 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 = 10000 nM (pChEMBL 5)
Descriptors: MW 388.47, ALogP 3.56, HBA 5, HBD 0, PSA 62.47, QED 0.69
Compound (SMILES): Cc1cc(C)nc(N2CC3CN(C(=O)c4ccccc4-c4nnc[nH]4)CC3C2)n1
InChIKey: NYDBXNHNMPHNGA-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Receptor Radioligand Binding Assay: HEK293 stably expressing human orexin-2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), in DMEM, 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 1×HEPES, 600 ug/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 just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moravek Corporation, specific activity=27 Ci/mmol), diluted to a 20 nM concentration in PBS (5 nM final concentration). 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 (N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylnaphthalene-1-carboxamide, CAS Registry #1089563-88-1). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA 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 = 2780 nM (pChEMBL 5.559999942779541)
Descriptors: MW 389.46, ALogP 2.09, HBA 6, HBD 1, PSA 90.9, QED 0.74
Compound (SMILES): Cc1cc(C)nc(N2CC3CN(C(=O)c4cccc(F)c4-n4nccn4)CC3C2)n1
InChIKey: RQCIXSIWGGVIAE-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Receptor Radioligand Binding Assay: HEK293 stably expressing human orexin-2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), in DMEM, 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 1×HEPES, 600 ug/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 just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moravek Corporation, specific activity=27 Ci/mmol), diluted to a 20 nM concentration in PBS (5 nM final concentration). 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 (N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylnaphthalene-1-carboxamide, CAS Registry #1089563-88-1). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA 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 = 1824 nM (pChEMBL 5.739999771118164)
Descriptors: MW 407.45, ALogP 2.02, HBA 7, HBD 0, PSA 80.04, QED 0.66