lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccnc(N2CC3CN(C(=O)c4c(C)ccc5ccccc45)CC3C2)n1
InChIKey: NSYQEJAIIUUYDV-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Receptor Radioligand Binding Assay: Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1× Pen/Strep, 600 μg/mL G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 10 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and vortexed for 45 sec prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-SB674042 (Moravek Corporation, specific activity=35.3 Ci/mmol), diluted to a 10 nM concentration in PBS (4 nM final). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentrations (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM (1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea, CAS Registry #288150-92-5). The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-5B674042 diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 372.47, ALogP 3.46, HBA 4, HBD 0, PSA 49.33, QED 0.69
Compound (SMILES): COc1ccnc(N2CC3CN(C(=O)c4ccccc4-c4cccc(F)c4)CC3C2)n1
InChIKey: OGHLIVQBOUOCAF-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 418.47, ALogP 3.5, HBA 5, HBD 0, PSA 58.56, QED 0.65
Compound (SMILES): Cc1cc(C)nc(N2CC3CN(C(=O)c4ccccc4-c4cccc(F)c4)CC3C2)n1
InChIKey: SJLACDBRLFYAGQ-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 = 8999 nM (pChEMBL 5.050000190734863)
Descriptors: MW 416.5, ALogP 4.11, HBA 4, HBD 0, PSA 49.33, QED 0.64
Compound (SMILES): Cc1cc(C)nc(N2CC3CN(C(=O)c4ccccc4F)CC3C2)n1
InChIKey: NQJPGCOBCMCROW-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 340.4, ALogP 2.44, HBA 4, HBD 0, PSA 49.33, QED 0.84
Compound (SMILES): COc1ccnc(N2CC3CN(C(=O)c4ccccc4-c4ccc(C)cc4)CC3C2)n1
InChIKey: FOQWGXBQBIJWCV-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 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 414.51, ALogP 3.67, HBA 5, HBD 0, PSA 58.56, QED 0.65
Compound (SMILES): COc1ccnc(N2CC3CN(C(=O)c4ccccc4-c4cccc(Cl)c4)CC3C2)n1
InChIKey: XIMJBEIRWFTLGH-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 = 744 nM (pChEMBL 6.130000114440918)
Descriptors: MW 434.93, ALogP 4.01, HBA 5, HBD 0, PSA 58.56, QED 0.62
Compound (SMILES): CCOc1ccc2ccccc2c1C(=O)N1CC2CN(c3nccc(OC)n3)CC2C1
InChIKey: PNKRSAGISOYJJQ-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 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 418.5, ALogP 3.25, HBA 6, HBD 0, PSA 67.79, QED 0.63
Compound (SMILES): COc1ccnc(N2CC3CN(C(=O)c4ccc(F)c5ccccc45)CC3C2)n1
InChIKey: UQOMQTRAYAAQIV-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 = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 392.43, ALogP 2.99, HBA 5, HBD 0, PSA 58.56, 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: Serine/threonine-protein kinase Nek2 (SINGLE PROTEIN), Homo sapiens
UniProt: P51955
Assay: Inhibition of NEK2 (unknown origin)
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
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: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
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 = 1.34 nM (pChEMBL 8.869999885559082)
Descriptors: MW 530.61, ALogP 4.41, HBA 9, HBD 5, PSA 147.55, QED 0.2
Compound (SMILES): COC(=O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O
InChIKey: LQWXMRRGVHUWEN-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 = 9900 nM (pChEMBL 5)
Descriptors: MW 320.73, ALogP 2.01, HBA 5, HBD 2, PSA 88.52, QED 0.84
Compound (SMILES): COC(=O)CNC(=O)c1ncc(-c2ccc(Cl)cc2)cc1O
InChIKey: BYGKIXAXITXFDW-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 > 100000 nM (pChEMBL 4)
Descriptors: MW 320.73, ALogP 2.01, HBA 5, HBD 2, PSA 88.52, QED 0.84
Compound (SMILES): Cc1ccc(-c2cnc(C(=O)NCC(=O)O)c(O)c2)cc1
InChIKey: VBNCAZJDNCXKIO-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H6Z9
Assay: Enzyme Assay: The EGLN-1 (or EGLN-3) enzyme activity is determined using mass spectrometry (matrix-assisted laser desorption ionization, time-of-flight MS, MALDI-TOF MS—for assay details, see reference (Greis et al., 2006).
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 286.29, ALogP 1.58, HBA 4, HBD 3, PSA 99.52, QED 0.79
Compound (SMILES): Cc1ccc(-c2ccc(C(=O)NCC(=O)O)c(O)c2)cc1
InChIKey: POKDHYRFSOQLCV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: VEGF ELISA Assay: HEK293 cells are seeded in 96-well poly-lysine coated plates at 20,000 ceils 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 Qpti-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.). Optical density measurements at 450 nm are recorded using the Spectra Max 250 (Molecular Devices, Sunnyvale, Calif.). Data defined as % of DFO stimulation is used to calculate EC50 values with GraphPad Prism 4 software (San Diego, Calif.).
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 285.3, ALogP 2.18, HBA 3, HBD 3, PSA 86.63, QED 0.8
Compound (SMILES): COC(=O)CNC(=O)c1ncc(-c2ccc(C)cc2)cc1O
InChIKey: DSAKFJKYBXTHSR-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 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 300.31, ALogP 1.67, HBA 5, HBD 2, PSA 88.52, QED 0.84
Compound (SMILES): COC(=O)CNC(=O)c1ncc(-c2ccccc2Cl)cc1O
InChIKey: BYSUDLAKLIQTEQ-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Enzyme Assay: The EGLN-1 (or EGLN-3) enzyme activity is determined using mass spectrometry (matrix-assisted laser desorption ionization, time-of-flight MS, MALDI-TOF MS—for assay details, see reference (Greis et al., 2006).
Measurement: IC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 320.73, ALogP 2.01, HBA 5, HBD 2, PSA 88.52, QED 0.84
Compound (SMILES): [C-]#[N+]c1ccc(-c2cnc(C(=O)NCC(=O)O)c(O)c2)cc1
InChIKey: WESRXHMJQHLLSE-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 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 297.27, ALogP 1.82, HBA 4, HBD 3, PSA 103.88, QED 0.75
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2ccc(Cl)cc2)cc1O
InChIKey: DLUPTLSWWQTJFJ-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H6Z9
Assay: Enzyme Assay: The EGLN-1 (or EGLN-3) enzyme activity is determined using mass spectrometry (matrix-assisted laser desorption ionization, time-of-flight MS, MALDI-TOF MS—for assay details, see reference (Greis et al., 2006).
Measurement: IC50 = 83 nM (pChEMBL 7.079999923706055)
Descriptors: MW 306.71, ALogP 1.92, HBA 4, HBD 3, PSA 99.52, QED 0.8
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 HIF-PHD2 using DLDLEALAPYIPADDDFQL as substrate after 20 mins by mass spectrometry
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 306.71, ALogP 1.92, HBA 4, HBD 3, PSA 99.52, QED 0.8
Compound (SMILES): CC(C)c1ccc(-c2cnc(C(=O)NCC(=O)O)c(O)c2)cc1
InChIKey: XZPLTNPEACHLGV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: VEGF ELISA Assay: HEK293 cells are seeded in 96-well poly-lysine coated plates at 20,000 ceils 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 Qpti-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.). Optical density measurements at 450 nm are recorded using the Spectra Max 250 (Molecular Devices, Sunnyvale, Calif.). Data defined as % of DFO stimulation is used to calculate EC50 values with GraphPad Prism 4 software (San Diego, Calif.).
Measurement: EC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 314.34, ALogP 2.39, HBA 4, HBD 3, PSA 99.52, QED 0.79
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2ccc(F)cc2)cc1O
InChIKey: XTAXWQIDORMKHA-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: VEGF ELISA Assay: HEK293 cells are seeded in 96-well poly-lysine coated plates at 20,000 ceils 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 Qpti-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.). Optical density measurements at 450 nm are recorded using the Spectra Max 250 (Molecular Devices, Sunnyvale, Calif.). Data defined as % of DFO stimulation is used to calculate EC50 values with GraphPad Prism 4 software (San Diego, Calif.).
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 290.25, ALogP 1.41, HBA 4, HBD 3, PSA 99.52, QED 0.79
Compound (SMILES): CC(C)Oc1ccc(-c2cnc(C(=O)NCC(=O)O)c(O)c2)cc1
InChIKey: XAQQOGZYOJAKKO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: VEGF ELISA Assay: HEK293 cells are seeded in 96-well poly-lysine coated plates at 20,000 ceils 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 Qpti-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.). Optical density measurements at 450 nm are recorded using the Spectra Max 250 (Molecular Devices, Sunnyvale, Calif.). Data defined as % of DFO stimulation is used to calculate EC50 values with GraphPad Prism 4 software (San Diego, Calif.).
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 330.34, ALogP 2.06, HBA 5, HBD 3, PSA 108.75, QED 0.75
Compound (SMILES): Cc1ccc(Cl)cc1-c1cnc(C(=O)NCC(=O)O)c(O)c1
InChIKey: XFZFCHHQSHMUBB-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: VEGF ELISA Assay: HEK293 cells are seeded in 96-well poly-lysine coated plates at 20,000 ceils 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 Qpti-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.). Optical density measurements at 450 nm are recorded using the Spectra Max 250 (Molecular Devices, Sunnyvale, Calif.). Data defined as % of DFO stimulation is used to calculate EC50 values with GraphPad Prism 4 software (San Diego, Calif.).
Measurement: EC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 320.73, ALogP 2.23, HBA 4, HBD 3, PSA 99.52, QED 0.8
Compound (SMILES): CNC(=O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O
InChIKey: FLEKXPKWSFKURA-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 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 319.75, ALogP 1.58, HBA 4, HBD 3, PSA 91.32, QED 0.8
Compound (SMILES): COC(=O)CNC(=O)c1ncc(-c2cccc(-c3nnn[nH]3)c2)cc1O
InChIKey: YSPBNSRKQJFWJL-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 > 100000 nM (pChEMBL 4)
Descriptors: MW 354.33, ALogP 0.54, HBA 8, HBD 3, PSA 142.98, QED 0.56
Compound (SMILES): COC(=O)CNC(=O)c1ncc(-c2cccc(C(N)=O)c2)cc1O
InChIKey: MWJDKCNAPFXDPO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: VEGF ELISA Assay: HEK293 cells are seeded in 96-well poly-lysine coated plates at 20,000 ceils 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 Qpti-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.). Optical density measurements at 450 nm are recorded using the Spectra Max 250 (Molecular Devices, Sunnyvale, Calif.). Data defined as % of DFO stimulation is used to calculate EC50 values with GraphPad Prism 4 software (San Diego, Calif.).
Measurement: EC50 = 50100 nM (pChEMBL 4.300000190734863)
Descriptors: MW 329.31, ALogP 0.46, HBA 6, HBD 3, PSA 131.61, QED 0.68
Compound (SMILES): COC(=O)CNC(=O)c1ncc(-c2cccc(C(=O)N3CCCC3)c2)cc1O
InChIKey: HBZHWXZOIFSLHR-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: VEGF ELISA Assay: HEK293 cells are seeded in 96-well poly-lysine coated plates at 20,000 ceils 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 Qpti-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.). Optical density measurements at 450 nm are recorded using the Spectra Max 250 (Molecular Devices, Sunnyvale, Calif.). Data defined as % of DFO stimulation is used to calculate EC50 values with GraphPad Prism 4 software (San Diego, Calif.).
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 383.4, ALogP 1.59, HBA 6, HBD 2, PSA 108.83, QED 0.76
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2cccc(C(=O)N3CCCC3)c2)cc1O
InChIKey: FPDULEQZUNAQKE-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: VEGF ELISA Assay: HEK293 cells are seeded in 96-well poly-lysine coated plates at 20,000 ceils 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 Qpti-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.). Optical density measurements at 450 nm are recorded using the Spectra Max 250 (Molecular Devices, Sunnyvale, Calif.). Data defined as % of DFO stimulation is used to calculate EC50 values with GraphPad Prism 4 software (San Diego, Calif.).
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 369.38, ALogP 1.5, HBA 5, HBD 3, PSA 119.83, QED 0.73
Compound (SMILES): O=C(O)CNC(=O)c1ncc(-c2cccc(-c3nnn[nH]3)c2)cc1O
InChIKey: JCWZYUTUSRZUAB-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: VEGF ELISA Assay: HEK293 cells are seeded in 96-well poly-lysine coated plates at 20,000 ceils 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 Qpti-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.). Optical density measurements at 450 nm are recorded using the Spectra Max 250 (Molecular Devices, Sunnyvale, Calif.). Data defined as % of DFO stimulation is used to calculate EC50 values with GraphPad Prism 4 software (San Diego, Calif.).
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 340.3, ALogP 0.45, HBA 7, HBD 4, PSA 153.98, QED 0.52
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C(C)CNCc1ccc(F)cc1F
InChIKey: ZLAHJDHBQQLJAB-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 = 21.4 nM (pChEMBL 7.670000076293945)
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)CNCc1c(F)cccc1F
InChIKey: HTLSXGHSMHEFSF-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 = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 480.98, ALogP 5.19, HBA 4, HBD 1, PSA 50.8, QED 0.54
Compound (SMILES): COc1ccccc1CNCC(C)C(=O)N(Cc1cc(Cl)c2c(c1)OCCCO2)CC(C)C
InChIKey: LLALWBCUMKNDNJ-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 = 0.72 nM (pChEMBL 9.140000343322754)
Descriptors: MW 475.03, ALogP 4.92, HBA 5, HBD 1, PSA 60.03, QED 0.53
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 = 178 nM (pChEMBL 6.75)
Descriptors: MW 445, ALogP 4.91, HBA 4, HBD 1, PSA 50.8, QED 0.6
Compound (SMILES): CC(C)CN(Cc1ccc2c(c1)OCCCO2)C(=O)CC(N)c1ccccc1
InChIKey: HFIRDMSUIREPSZ-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 = 1162 nM (pChEMBL 5.929999828338623)
Descriptors: MW 382.5, ALogP 3.92, HBA 4, HBD 1, PSA 64.79, QED 0.79
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C1CCN(Cc2cccc3c2ccn3C)C1
InChIKey: YUOQDCRTZDLQDD-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 = 3.64 nM (pChEMBL 8.4399995803833)
Descriptors: MW 510.08, ALogP 5.5, HBA 5, HBD 0, PSA 46.94, QED 0.42
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)C1CCN(Cc2cccc3c2OCCO3)C1
InChIKey: VVUZVKZRRVISEK-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 = 6.88 nM (pChEMBL 8.15999984741211)
Descriptors: MW 515.05, ALogP 4.78, HBA 6, HBD 0, PSA 60.47, QED 0.53
Compound (SMILES): COc1ccccc1CN1CC[C@@H](C(=O)N(Cc2ccc3c(c2)OCCCO3)CC(C)C)C1
InChIKey: BYGDYIHRENEMPP-HSZRJFAPSA-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 = 2.67 nM (pChEMBL 8.569999694824219)
Descriptors: MW 452.6, ALogP 4.36, HBA 5, HBD 0, PSA 51.24, QED 0.6
Compound (SMILES): COc1ccccc1CN1CC[C@@H](C(=O)N(Cc2cc(Cl)c3c(c2)OCCCO3)CC(C)C)C1
InChIKey: MNALEGAPZJRICC-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 = 8.8 nM (pChEMBL 8.0600004196167)
Descriptors: MW 487.04, ALogP 5.02, HBA 5, HBD 0, PSA 51.24, QED 0.52
Compound (SMILES): COc1ccccc1CN1CC[C@@H](C(=O)N(Cc2cc(F)c3c(c2)OCCCO3)CC(C)C)C1
InChIKey: LWIUAAFMSATBNR-JOCHJYFZSA-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 = 0.81 nM (pChEMBL 9.09000015258789)
Descriptors: MW 470.59, ALogP 4.5, HBA 5, HBD 0, PSA 51.24, QED 0.57
Compound (SMILES): Cc1ccccc1CN1CCCC(C(=O)N(Cc2cc(Cl)c3c(c2)OCCCO3)CC(C)C)C1
InChIKey: JEKKOWNAXUJQAB-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 = 29.2 nM (pChEMBL 7.539999961853027)
Descriptors: MW 485.07, ALogP 5.71, HBA 4, HBD 0, PSA 42.01, QED 0.5
Compound (SMILES): Cc1ccccc1CN1CC[C@@H](C(=O)N(Cc2cc(F)c3c(c2)OCCCO3)CC(C)C)C1
InChIKey: UAMHNXUVDALRMY-HSZRJFAPSA-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 = 17.5 nM (pChEMBL 7.760000228881836)
Descriptors: MW 454.59, ALogP 4.8, HBA 4, HBD 0, PSA 42.01, QED 0.6
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)[C@@H]1CCN(Cc2cccc(O)c2)C1
InChIKey: PAZVPMAPHLXERX-OAQYLSRUSA-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 = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 473.01, ALogP 4.71, HBA 5, HBD 1, PSA 62.24, QED 0.63
Compound (SMILES): CC(C)CN(Cc1cc(Cl)c2c(c1)OCCCO2)C(=O)[C@@H]1CCN(Cc2cccc3cc[nH]c23)C1
InChIKey: ZAFNXORCJWUJHJ-HSZRJFAPSA-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 = 1.22 nM (pChEMBL 8.90999984741211)
Descriptors: MW 496.05, ALogP 5.49, HBA 4, HBD 1, PSA 57.8, QED 0.47
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 = 31.2 nM (pChEMBL 7.510000228881836)
Descriptors: MW 457.01, ALogP 5.01, HBA 4, HBD 0, PSA 42.01, QED 0.59
Compound (SMILES): CC(C)CN(Cc1cc(F)c2c(c1)OCCCO2)C(=O)[C@@H]1CCN(Cc2ccccc2)C1
InChIKey: NBPVAEHPCIAALG-JOCHJYFZSA-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 = 18.3 nM (pChEMBL 7.739999771118164)
Descriptors: MW 440.56, ALogP 4.49, HBA 4, HBD 0, PSA 42.01, QED 0.64
Compound (SMILES): COc1ncccc1CN1CC[C@@H](C(=O)N(Cc2cc(Cl)c3c(c2)OCCCO3)CC(C)C)C1
InChIKey: LZHHPZAUVGQCSX-OAQYLSRUSA-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 = 5.34 nM (pChEMBL 8.270000457763672)
Descriptors: MW 488.03, ALogP 4.41, HBA 6, HBD 0, PSA 64.13, QED 0.55
Compound (SMILES): CCc1ccccc1CNCC(C)C(=O)N(Cc1cc(Cl)c2c(c1)OCCCO2)CC(C)C
InChIKey: PLCCRKPQVGHIOJ-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 = 31.4 nM (pChEMBL 7.5)
Descriptors: MW 473.06, ALogP 5.47, HBA 4, HBD 1, PSA 50.8, QED 0.5