lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C2CCCCCCCCCC2)c1=O
InChIKey: YQRPDABJJCVAGZ-ZBYYUNFXSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Radioligand Binding Assay: Radioligand dose-displacement assays used 0.2nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20ug membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 500uL binding buffer (5mM MgCl2, 5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 uM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined 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 five filtration washes with 500uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 451.61, ALogP 5.55, HBA 5, HBD 1, PSA 75.43, QED 0.66
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 > 20000 nM (pChEMBL 4.698999881744385)
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: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
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 = 1.1 nM (pChEMBL 8.960000038146973)
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 = 76 nM (pChEMBL 7.119999885559082)
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 Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of TEC (unknown origin) by FRET assay
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
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: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
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 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 454.53, ALogP 4.65, HBA 7, HBD 2, PSA 107.95, QED 0.41
Compound (SMILES): C=CC(=O)N1CCC(n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: KALPRSFUZYGTNU-UHFFFAOYSA-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 = 60.9 nM (pChEMBL 7.210000038146973)
Descriptors: MW 440.51, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.47
Compound (SMILES): c1ccc(CN2CC3CCC2C3Nc2ccc3[nH]ncc3c2)cc1
InChIKey: UTVPCECSRXIEDH-UHFFFAOYSA-N
Target: Rho GDP-dissociation inhibitor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P52565
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 = 976 nM (pChEMBL 6.010000228881836)
Descriptors: MW 318.42, ALogP 3.64, HBA 3, HBD 2, PSA 43.95, QED 0.77
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 180 nM (pChEMBL 6.75)
Descriptors: MW 505.55, ALogP -1.03, HBA 8, HBD 6, PSA 200.77, QED 0.12
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 505.55, ALogP -1.03, HBA 8, HBD 6, PSA 200.77, QED 0.12
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 21 nM (pChEMBL 7.679999828338623)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 340 nM (pChEMBL 6.46999979019165)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 280 nM (pChEMBL 6.550000190734863)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 21 nM (pChEMBL 7.679999828338623)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 581.7, ALogP 1.16, HBA 7, HBD 6, PSA 183.7, 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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 20 nM (pChEMBL 7.699999809265137)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 350 nM (pChEMBL 6.460000038146973)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 210 nM (pChEMBL 6.679999828338623)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 110 nM (pChEMBL 6.960000038146973)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 410 nM (pChEMBL 6.389999866485596)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 6.8 nM (pChEMBL 8.170000076293945)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 4.7 nM (pChEMBL 8.329999923706055)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 180 nM (pChEMBL 6.75)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
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: Serine protease 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P00762
Assay: Enzyme Assay: Inhibition constant of the compound against Trypsin
Measurement: Ki = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 505.55, ALogP -1.19, HBA 7, HBD 7, PSA 211.77, QED 0.13
Compound (SMILES): CC(C)(C)OC(=O)c1ccc(-n2[nH]cc(-n3ccnn3)c2=O)nc1
InChIKey: HWQQDVNGHZIALS-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 = 5100 nM (pChEMBL 5.289999961853027)
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 4-hydroxylase (SINGLE PROTEIN), Paramecium bursaria Chlorella virus 1
UniProt: Q84406
Assay: Inhibition of N-terminal His6-tagged recombinant Paramecium bursaria chlorella virus 1 CPH expressed in Escherichia coli Rosetta 2 (DE3) cells pre-incubated for 5 mins before 2OG as substrate and Fe2 as co-factor addition in presence of L-ascorbate and measured after 5 mins MALDI TOF MS analysis
Measurement: Ki = 16050 nM (pChEMBL 4.789999961853027)
Descriptors: MW 314.31, ALogP -0.63, HBA 9, HBD 1, PSA 106.75, QED 0.69
Compound (SMILES): Cc1cccc(NC(=O)Nc2ccc(-c3csc4c(-c5cnn(C[C@H](C)O)c5)cnc(N)c34)cc2)c1
InChIKey: VKBFHTIUXUCYRQ-KRWDZBQOSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution.
Measurement: IC50 = 2.18 nM (pChEMBL 8.65999984741211)
Descriptors: MW 498.61, ALogP 5.74, HBA 7, HBD 4, PSA 118.09, QED 0.24
Compound (SMILES): COc1ccc(NC(=O)Nc2ccc(-c3csc4c(-c5cnn(C[C@H](O)CO)c5)cnc(N)c34)cc2)cc1
InChIKey: BRTHUECZMVKNMQ-FQEVSTJZSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution.
Measurement: IC50 = 12.58 nM (pChEMBL 7.900000095367432)
Descriptors: MW 530.61, ALogP 4.41, HBA 9, HBD 5, PSA 147.55, QED 0.2
Compound (SMILES): Cc1ccc(-c2cnc(C(=O)NCC(=O)O)c(O)c2)cc1
InChIKey: VBNCAZJDNCXKIO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: HEK293 cells are seeded in 96-well poly-lysine coated plates at 20,000 cells per well in DMEM (10% FBS, 1% NEAA, 0.1% glutamine). Following overnight incubation, the cells are washed with 100 uL of Opti-MEM (Gibco, Carlsbad, Calif.) to remove serum. Compound in DMSO is serially diluted (beginning with 100 μM) in Opti-MEM and added to the cells. The conditioned media is analyzed for VEGF with a Quantikine human VEGF immunoassay kit (R&D Systems, Minneapolis, Minn.).
Measurement: EC50 = 42100 nM (pChEMBL 4.380000114440918)
Descriptors: MW 286.29, ALogP 1.58, HBA 4, HBD 3, PSA 99.52, QED 0.79
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O
InChIKey: JGRXMPYUTJLTKT-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Inhibition of recombinant human PHD2 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 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 306.71, ALogP 1.92, HBA 4, HBD 3, PSA 99.52, QED 0.8
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1ccc(F)cc1F
InChIKey: ZLAHJDHBQQLJAB-UHFFFAOYSA-N
Target: Prokineticin receptor 1 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3HIE5
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 480.98, ALogP 5.19, HBA 4, HBD 1, PSA 50.8, QED 0.54
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1ccccc1
InChIKey: GGHVZCHFXLKKQW-UHFFFAOYSA-N
Target: Prokineticin receptor 2 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3H407
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 4.92 nM (pChEMBL 8.3100004196167)
Descriptors: MW 445, ALogP 4.91, HBA 4, HBD 1, PSA 50.8, QED 0.6
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)[C@@H]1CCN(Cc2ccccc2)C1
InChIKey: IOXBZEKQVLIIQH-JOCHJYFZSA-N
Target: Prokineticin receptor 1 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3HIE5
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 457.01, ALogP 5.01, HBA 4, HBD 0, PSA 42.01, QED 0.59
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1cccc2c1OCC2
InChIKey: TYDAFIIHYGCPNJ-UHFFFAOYSA-N
Target: Prokineticin receptor 2 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3H407
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 2.28 nM (pChEMBL 8.640000343322754)
Descriptors: MW 487.04, ALogP 4.85, HBA 5, HBD 1, PSA 60.03, QED 0.55
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1cccc2[nH]ccc12
InChIKey: WVARBMDYVFPBSM-UHFFFAOYSA-N
Target: Prokineticin receptor 1 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3HIE5
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 484.04, ALogP 5.39, HBA 4, HBD 2, PSA 66.59, QED 0.43
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1cccc2cc[nH]c12
InChIKey: KAPDWKOAFWYLSJ-UHFFFAOYSA-N
Target: Prokineticin receptor 1 (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3HIE5
Assay: Calcium Mobilization Assay: An aequorin-based luminescent assay for calcium mobilization was used to measure mobilization of intracellular Ca2+ (Bullock et al., Mol Pharmacol 65, 582-588, 2004). Chinese hamster ovary (CHO) cells stably expressing photoprotein aequorin and recombinant PKR1 or PKR2 were tested by this method. Briefly, the cells were charged in Opti-MEM (Invitrogen) containing 8 μM of coelenterazine cp at 37° C. for 2 hours. Cells were detached by brief typsinization and maintained in Hank's Balanced Salt Solution (HBSS) plus 10 mM HEPES (pH7.5) and 0.1% BSA at about 5×105 cells/ml. Luminescence measurements were made using a Berthold luminometer.
Measurement: Ki = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 484.04, ALogP 5.39, HBA 4, HBD 2, PSA 66.59, QED 0.43
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCCNC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: SUYDUGVDUFCDHQ-IQSCWYJSSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 1058.22
Compound (SMILES): CC(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1CCCNC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: SUYDUGVDUFCDHQ-XEFNOBGUSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 1058.22
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCCNC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: BOAIJXQJMLWMSF-VWUVXGKKSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 1044.19
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCCCNC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: GTMASPVXPKDKOK-VWUVXGKKSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 1044.19
Compound (SMILES): CC(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1CCCNC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: BOAIJXQJMLWMSF-GWZAZKCQSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: cAMP Assay: Accumulation of intracellular cAMP was examined as a measure of the ability of the peptides of the present invention to elicit a functional response in HEK-293 cells that express MC4-R. Confluent HEK-293 cells that express recombinant hMC4-R were detached from culture plates by incubation in enzyme-free cell dissociation buffer. Dispersed cells were suspended in Earle's Balanced Salt Solution containing 10 mM HEPES (pH 7.5), 1 mM MgCl2, 1 mM glutamine, 0.5% albumin and 0.3 mM 3-isobutyl-1-methyl-xanthine (IBMX), a phosphodiesterase inhibitor. The cells were plated in 96-well plates at a density of 0.5x105 cells per well and pre-incubated for 10 minutes. Cells were exposed for 15 minutes at 37° C. to peptides of the present invention dissolved in DMSO (final DMSO concentration of 1%) at a concentration range of 0.05-5000 nM in a total assay volume of 200 uL. NDP-α-MSH was used as the reference agonist. cAMP levels were determined by an HTRF cAMP cell-based assay system from Cisbio Bioassays utilizing cryptate-labeled anti-cAMP and d2-labeled cAMP, with plates read on a PerkinElmer Victor plate reader at 665 and 620 nM. Data analysis was performed by nonlinear regression analysis with Graph-Pad Prism software. The maximum efficacies of the test peptides of the present invention were compared to that achieved by the reference melanocortin agonist NDP-αMSH.
Measurement: EC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 1044.19
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCNC(=O)CCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: FSTDLRINZOKGRA-IQSCWYJSSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: cAMP Assay: Accumulation of intracellular cAMP was examined as a measure of the ability of the peptides of the present invention to elicit a functional response in HEK-293 cells that express MC4-R. Confluent HEK-293 cells that express recombinant hMC4-R were detached from culture plates by incubation in enzyme-free cell dissociation buffer. Dispersed cells were suspended in Earle's Balanced Salt Solution containing 10 mM HEPES (pH 7.5), 1 mM MgCl2, 1 mM glutamine, 0.5% albumin and 0.3 mM 3-isobutyl-1-methyl-xanthine (IBMX), a phosphodiesterase inhibitor. The cells were plated in 96-well plates at a density of 0.5x105 cells per well and pre-incubated for 10 minutes. Cells were exposed for 15 minutes at 37° C. to peptides of the present invention dissolved in DMSO (final DMSO concentration of 1%) at a concentration range of 0.05-5000 nM in a total assay volume of 200 uL. NDP-α-MSH was used as the reference agonist. cAMP levels were determined by an HTRF cAMP cell-based assay system from Cisbio Bioassays utilizing cryptate-labeled anti-cAMP and d2-labeled cAMP, with plates read on a PerkinElmer Victor plate reader at 665 and 620 nM. Data analysis was performed by nonlinear regression analysis with Graph-Pad Prism software. The maximum efficacies of the test peptides of the present invention were compared to that achieved by the reference melanocortin agonist NDP-αMSH.
Measurement: EC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 1058.22
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCCC(=O)NCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: ZLLOVWBBACAVIV-VWUVXGKKSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 295 nM (pChEMBL 6.53000020980835)
Descriptors: MW 1044.19
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCC(=O)NCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: HYNXKHHGAXLIEQ-VWUVXGKKSA-N
Target: Melanin-concentrating hormone receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99705
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-α-MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl, 2 mM CaCl2, 2 mM MgCl2, 0.3 mM 1,10-phenanthroline, and 0.2% bovine serum albumin. After incubation for 60 minutes at 37° C., the assay mixture was filtered and the membranes washed three times with ice-cold buffer. Filters were dried and counted in a gamma counter for bound radioactivity. Non-specific binding was measured by inhibition of binding of [I125]-NDP-α-MSH in the presence of 1 μM NDP-α-MSH. Maximal specific binding (100%) was defined as the difference in radioactivity (cpm) bound to cell membranes in the absence and presence of 1 μM NDP-α-MSH. Radioactivity (cpm) obtained in the presence of test compounds was normalized with respect to 100% specific binding to determine the percent inhibition of [I125]-NDP-α-MSH binding.
Measurement: Ki = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 1044.19
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCCCNC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: KOMGNGDDTPNSKC-PDBPWWFNSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: cAMP Assay: Accumulation of intracellular cAMP was examined as a measure of the ability of the peptides of the present invention to elicit a functional response in HEK-293 cells that express MC4-R. Confluent HEK-293 cells that express recombinant hMC4-R were detached from culture plates by incubation in enzyme-free cell dissociation buffer. Dispersed cells were suspended in Earle's Balanced Salt Solution containing 10 mM HEPES (pH 7.5), 1 mM MgCl2, 1 mM glutamine, 0.5% albumin and 0.3 mM 3-isobutyl-1-methyl-xanthine (IBMX), a phosphodiesterase inhibitor. The cells were plated in 96-well plates at a density of 0.5x105 cells per well and pre-incubated for 10 minutes. Cells were exposed for 15 minutes at 37° C. to peptides of the present invention dissolved in DMSO (final DMSO concentration of 1%) at a concentration range of 0.05-5000 nM in a total assay volume of 200 uL. NDP-α-MSH was used as the reference agonist. cAMP levels were determined by an HTRF cAMP cell-based assay system from Cisbio Bioassays utilizing cryptate-labeled anti-cAMP and d2-labeled cAMP, with plates read on a PerkinElmer Victor plate reader at 665 and 620 nM. Data analysis was performed by nonlinear regression analysis with Graph-Pad Prism software. The maximum efficacies of the test peptides of the present invention were compared to that achieved by the reference melanocortin agonist NDP-αMSH.
Measurement: EC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 1055.21
Compound (SMILES): C[C@H]1CC[C@H](Cn2c(N3CCO[C@@H]4CCC[C@H]43)nc3cc(-c4noc(=O)[nH]4)nc(-c4cncc(Cl)c4)c32)CC1
InChIKey: FDBWTMMKIZGUEZ-IEGYKGNPSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Activation of CYP3A4 (unknown origin)
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 550.06, ALogP 5.07, HBA 9, HBD 1, PSA 114.96, QED 0.37
Compound (SMILES): C[C@H]1CC[C@H](Cn2c(N3CCCC4CCCC43)nc3cc(-c4noc(=O)[nH]4)nc(-c4cncc(Cl)c4)c32)CC1
InChIKey: CJKBAYXWIIJQPF-VMXWJKLDSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 548.09, ALogP 6.09, HBA 8, HBD 1, PSA 105.73, QED 0.32
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/[C@H]1CCCN1C
InChIKey: SADXACCFNXBCFY-IYNHSRRRSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 D769Y mutant (unknown origin) incubated for 120 mins in presence of 33P-ATP by P81 ion exchange cellulose chromatography
Measurement: IC50 = 57.36 nM (pChEMBL 7.239999771118164)
Descriptors: MW 583.09, ALogP 6.47, HBA 8, HBD 2, PSA 112.4, QED 0.2
Compound (SMILES): CCOC(=O)CNC(=O)NCc1ccc(N)cc1
InChIKey: UCMPTJMHPJQEED-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08752
Assay: Inhibition of Cyclophilin D (unknown origin) activity preincubated for 15 mins followed Suc-AAPF-pNA substrate addition by chymotrypsin coupled based spectrophotometry assay
Measurement: Ki = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 251.29, ALogP 0.63, HBA 4, HBD 3, PSA 93.45, QED 0.53
Compound (SMILES): Cc1nn(C2CCCCC2)c2sc(C(=O)Nc3ccc(N4CCC(O)CC4)cc3)cc12
InChIKey: QMTADOHBGLSRDC-UHFFFAOYSA-N
Target: Phosphodiesterase 4B (SINGLE PROTEIN), Mus musculus
UniProt: Q8VBU5
Assay: Inhibition Assay: The PDE 4 (phosphodiesterase IV) inhibiting effect of the compounds of the present invention was performed by the following method, which was modified assay method described in Biochemical. Pharmacol. 48(6), 1219-1223 (1994).  (1) The active fraction of PDE 4 (phosphodiesterase IV) was obtained. That is, the livers obtained from three Balb/c mice (male, 12 weeks: obtainable from CLEA Japan, Inc.) were suspended with 30 mL of buffer solution B [20 mM of bis-tris, 5 mM of 2-mercaptoethnol, 2 mM of benzamidine, 2 mM of EDTA, 0.1 mM of 4-(2-aminoethyl)benzensulfonyl hydrochloride, 50 mM of sodium acetate; pH 6.5], then homogenized by Polytron homogenizer. The homogenate were centrifuged under 25,000xG for 10 minutes at 4 C. The supernatant was separated and thus obtained supernatant was further centrifuged under 100,000xG for 60 minutes at 4Â° C., and then filtrated with 0.2 um filter to obtain the soluble fraction.
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 438.6, ALogP 5.12, HBA 6, HBD 2, PSA 70.39, QED 0.59
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)CC)cc4OC)c3)cnnc21
InChIKey: PTTQXDBPTFOCMT-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 = 77000 nM (pChEMBL 4.110000133514404)
Descriptors: MW 440.5, ALogP 4.12, HBA 7, HBD 0, PSA 86.97, QED 0.45
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2ccncc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](NC[C@H](Cc2ccc(O)cc2)NC(=O)CSC[C@@H]2C[C@@H]3c4cccc5[nH]cc(c45)C[C@H]3N(C)C2)CCCCNC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: PTIFFBYOEZNBTJ-BGUUXQBZSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Radioligand Binding Assay: Membranes for in vitro receptor binding assays were obtained by the following procedures. CHO-K1 cells expressing one of the somatostatin receptors were homogenized in ice-cold buffer with 10 mM Tris-HCl, 5 mM EDTA, 3 mM EGTA, 1 mM phenylmethylsuphonyl fluoride, pH 7.6, using Polytron PT10-35GT (Kinematica) at 18,000 rpm for 30 seconds and centrifuged at 500xg for 10 minutes. The supernatant containing the plasma membranes was centrifuged at 100,000xg for 30 minutes and the pellet was resuspended in buffer containing 20 mM glycine-glycine, 1 mM MgCl2, 250 mM sucrose, pH 7.2, for storage at -80 C.For the SSTR1, 2 and 5 assays, membranes and various concentrations of test compounds were incubated in 96-well plates for 60 minutes at 25 C. with 0.05 nM [125I-Tyr11]-SRIF-14 (for hSSTR1; PerkinElmer Life Science), 0.05 nM [125I-Tyr]-seglitide (for hSSTR2; PerkinElmer Life Science) or 0.05 nM [125I-Tyr]-[DPhe-cyclo(Cys-Tyr-DTrp-Lys-Val-Cys)-Thr-NH2] (for hSSTR5.
Measurement: Ki = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 1604.01