lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)c1ccc(Cn2nc3c(c2Nc2ccc(F)c(F)c2)C(=O)N(C)C2=NC(C)(C)CN23)cc1
InChIKey: ITYGOFCAYSOSFS-UHFFFAOYSA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P54750
Assay: Enzyme Assay: Materials: All chemicals are available from Sigma-Aldrich (St. Louis, Mo.) except for IMAP reagents (reaction buffer, binding buffer, FL-GMP and IMAP beads), which are available from Molecular Devices (Sunnyvale, Calif.).Assay: The following phosphodiesterase enzymes may be used: 3',5'-cyclic-nucleotide-specific bovine brain phosphodiesterase (Sigma, St. Louis, Mo.) and recombinant full length human PDE1A and PDE1B (r-hPDE1A and r-hPDE1B, respectively) which may be produced e.g., in HEK or SF9 cells by one skilled in the art. The PDE1 enzyme is reconstituted with 50% glycerol to 2.5 U/ml. One unit of enzyme will hydrolyze 1.0 umole of 3',5'-cAMP to 5'-AMP per min at pH 7.5 at 30 C. One part enzyme is added to 1999 parts reaction buffer (30 uM CaCl2, 10 U/ml of calmodulin (Sigma P2277), 10 mM Tris-HCl pH 7.2, 10 mM MgCl2, 0.1% BSA, 0.05% NaN3) to yield a final concentration of 1.25 mU/ml. 99 ul of diluted enzyme solution is added into each assay.
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 478.5, ALogP 4.2, HBA 7, HBD 1, PSA 82.83, QED 0.56
Compound (SMILES): CC(=O)c1ccc(Cn2nc3c(c2Nc2ccc(F)c(C)c2)C(=O)N(C)C2=NC(C)(C)CN23)cc1
InChIKey: KQMWFBJUYHOBDC-UHFFFAOYSA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P54750
Assay: Enzyme Assay: Materials: All chemicals are available from Sigma-Aldrich (St. Louis, Mo.) except for IMAP reagents (reaction buffer, binding buffer, FL-GMP and IMAP beads), which are available from Molecular Devices (Sunnyvale, Calif.).Assay: The following phosphodiesterase enzymes may be used: 3',5'-cyclic-nucleotide-specific bovine brain phosphodiesterase (Sigma, St. Louis, Mo.) and recombinant full length human PDE1A and PDE1B (r-hPDE1A and r-hPDE1B, respectively) which may be produced e.g., in HEK or SF9 cells by one skilled in the art. The PDE1 enzyme is reconstituted with 50% glycerol to 2.5 U/ml. One unit of enzyme will hydrolyze 1.0 umole of 3',5'-cAMP to 5'-AMP per min at pH 7.5 at 30 C. One part enzyme is added to 1999 parts reaction buffer (30 uM CaCl2, 10 U/ml of calmodulin (Sigma P2277), 10 mM Tris-HCl pH 7.2, 10 mM MgCl2, 0.1% BSA, 0.05% NaN3) to yield a final concentration of 1.25 mU/ml. 99 ul of diluted enzyme solution is added into each assay.
Measurement: Ki = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 474.54, ALogP 4.37, HBA 7, HBD 1, PSA 82.83, QED 0.56
Compound (SMILES): [C-]#[N+]C1=C(C)Nc2oncc2C1c1ccc2[nH]nc(C)c2c1
InChIKey: AWQHXAVNPINXQJ-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Homogeneous Time-Resolved Fluorescence Assay: The N-terminally His6-tagged recombinant kinase domain of the human c-Met (amino acids 960-1390), expressed in insect cells (SF21) and purified by Ni-NTA affinity chromatography and consecutive size exclusion chromatography (Superdex 200), is used. Alternatively, commercially available c-Met (Millipore) can be used. As substrate for the kinase reaction, the biotinylated polyGlu,Tyr (4:1) copolymer (#61GT0BLC, Cis Biointernational, Marcoule, France) is used. For the assay, 50 mL of a 100-fold concentrated solution of the test compound in DMSO is pipetted into a black low-volume 384-well microtiter plate (Greiner Bio-One, Frickenhausen, Germany). 2 uL of a solution of c-Met in assay buffer [25 mM Hepes/NaOH, pH 7.5; 5 mM MgCl2; 5 mM MnCl2; 2 mM dithiothreitol; 0.1% (v/v) Tween 20 (Sigma); 0.1% (w/v) bovine serum albumin] are added, and the mixture is incubated for 15 min at 22 C. to allow pre-binding of the test compound to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 291.31, ALogP 3.57, HBA 4, HBD 2, PSA 71.1, QED 0.67
Compound (SMILES): [C-]#[N+]C1=C(C)Nc2onc(C)c2C1c1cc2c(C)n[nH]c2cc1F
InChIKey: MQFDMOPYKXZYLJ-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Homogeneous Time-Resolved Fluorescence Assay: The N-terminally His6-tagged recombinant kinase domain of the human c-Met (amino acids 960-1390), expressed in insect cells (SF21) and purified by Ni-NTA affinity chromatography and consecutive size exclusion chromatography (Superdex 200), is used. Alternatively, commercially available c-Met (Millipore) can be used. As substrate for the kinase reaction, the biotinylated polyGlu,Tyr (4:1) copolymer (#61GT0BLC, Cis Biointernational, Marcoule, France) is used. For the assay, 50 mL of a 100-fold concentrated solution of the test compound in DMSO is pipetted into a black low-volume 384-well microtiter plate (Greiner Bio-One, Frickenhausen, Germany). 2 uL of a solution of c-Met in assay buffer [25 mM Hepes/NaOH, pH 7.5; 5 mM MgCl2; 5 mM MnCl2; 2 mM dithiothreitol; 0.1% (v/v) Tween 20 (Sigma); 0.1% (w/v) bovine serum albumin] are added, and the mixture is incubated for 15 min at 22 C. to allow pre-binding of the test compound to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 323.33, ALogP 4.02, HBA 4, HBD 2, PSA 71.1, QED 0.66
Compound (SMILES): CC(=O)c1cn(CC(=O)N2C[C@H](F)C[C@H]2C(=O)NCc2cccc(Cl)c2F)c2cc(O)ccc12
InChIKey: KHPAOTIUDMLXII-VFNWGFHPSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: In Vitro Assay: Recombinant human factor D (expressed in E. coli and purified using standard methods) at 10 nM concentration is incubated with test compound at various concentrations for 1 hour at room temperature in 0.1 M Hepes buffer, pH 7.5, containing 1 mM MgCl2, 1 M NaCl and 0.05% CHAPS. A synthetic substrate Z-Lys-thiobenzyl and 2,4-dinitrobenzenesulfonyl-fluoresceine are added to final concentrations of 200 μM and 25 μM, respectively. The increase in fluorescence is recorded at excitation of 485 nm and emission at 535 nm in a microplate spectrofluorimeter. IC50 values are calculated from percentage of inhibition of complement factor D-activity as a function of test compound concentration.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 489.91, ALogP 3.6, HBA 5, HBD 2, PSA 91.64, QED 0.52
Compound (SMILES): NC(=O)c1nn(CC(=O)N2[C@@H]3C[C@@H]3C[C@H]2C(=O)Nc2cccc(Br)c2F)c2ccccc12
InChIKey: CBUWZKCTGVDHDO-LQAWEQHXSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of complement factor D in human whole blood assessed as decrease in zymosan-induced AP activation mediated soluble MAC complex formation preincubated for 15 mins followed by zymosan addition measured after 40 mins by ELISA
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 500.33, ALogP 2.66, HBA 5, HBD 2, PSA 110.32, QED 0.56
Compound (SMILES): C[C@H](NC(=O)[C@@H]1C[C@H]2C[C@H]2N1C(=O)Cn1nc(C(N)=O)c2ccncc21)c1cccc(Cl)c1F
InChIKey: YAALCKJNOOFODD-SONRMIBWSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of factor D in human serum assessed as decrease in lysis of human erythrocytes after 1 hr
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 484.92, ALogP 2.19, HBA 6, HBD 2, PSA 123.21, QED 0.55
Compound (SMILES): C[C@@H](NC(=O)[C@@H]1C[C@H]2C[C@H]2N1C(=O)Cn1nc(C(N)=O)c2ccncc21)c1cccc(Cl)c1F
InChIKey: YAALCKJNOOFODD-SKNMWMDOSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 484.92, ALogP 2.19, HBA 6, HBD 2, PSA 123.21, QED 0.55
Compound (SMILES): NC(=O)c1nn(CC(=O)N2[C@@H]3C[C@@H]3C[C@H]2C(=O)NCc2cccc(Cl)c2F)c2cnccc12
InChIKey: ZCXXWKVJUVYAMI-WQVCFCJDSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition Assay: Human factor D (purified from human serum, Complement Technology, Inc.) at 80 nM final concentration is incubated with test compound at various concentrations for 5 minutes at room temperature in 50 mM Tris, 1M NaCl, pH 7.5. A synthetic substrate Z-L-Lys-SBzl and DTNB (Ellman's reagent) are added to final concentrations of 10 μM each. The increase in color is recorded at OD405 nm in a microplate in kinetic mode over 30 minutes with 30 second time points in a spectrofluorimeter. IC50 values are calculated by non-linear regression from the percentage of inhibition of complement factor D activity as a function of test compound concentration.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 470.89, ALogP 1.63, HBA 6, HBD 2, PSA 123.21, QED 0.57
Compound (SMILES): CC(C)n1c(Nc2ccccc2)nc2cnc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3)nc21
InChIKey: FXJYGGNAOIGUCL-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 484.61, ALogP 4.72, HBA 8, HBD 3, PSA 100, QED 0.35
Compound (SMILES): CC(C)n1c(Nc2cccc(Br)c2)nc2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc21
InChIKey: NYBSAZXOBAFBSJ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 521.47, ALogP 5.41, HBA 8, HBD 2, PSA 74.14, QED 0.35
Compound (SMILES): C#Cc1cccc(Nc2nc3cnc(Nc4ccc(N5CCN(C)CC5)cc4)nc3n2C(C)C)c1
InChIKey: UHUCLHAHTSRPSQ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 466.59, ALogP 4.63, HBA 8, HBD 2, PSA 74.14, QED 0.4
Compound (SMILES): CC(C)n1c(Nc2ccc(F)c(Cl)c2)nc2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc21
InChIKey: DACSXLTVEKOFCW-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 495.01, ALogP 5.44, HBA 8, HBD 2, PSA 74.14, QED 0.37
Compound (SMILES): CC(C)n1c(Nc2ccc(Br)cc2)nc2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc21
InChIKey: YLRQTRNCNYEOFF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 521.47, ALogP 5.41, HBA 8, HBD 2, PSA 74.14, QED 0.35
Compound (SMILES): CC(C)n1c(Nc2cccc(C(F)(F)F)c2)nc2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc21
InChIKey: WBIXSULLIITHLG-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 510.57, ALogP 5.67, HBA 8, HBD 2, PSA 74.14, QED 0.35
Compound (SMILES): COc1cccc(Nc2nc3cnc(Nc4ccc(N5CCN(C)CC5)cc4)nc3n2C(C)C)c1
InChIKey: RPHNDUBGTOJBFI-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 472.6, ALogP 4.65, HBA 9, HBD 2, PSA 83.37, QED 0.4
Compound (SMILES): COc1ccc(Nc2nc3cnc(Nc4ccc(N5CCN(C)CC5)cc4)nc3n2C(C)C)cc1
InChIKey: VHHKVHHSKBHBAO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 472.6, ALogP 4.65, HBA 9, HBD 2, PSA 83.37, QED 0.4
Compound (SMILES): CC(C)n1c(Nc2ccc(OCc3cccc(F)c3)c(Cl)c2)nc2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc21
InChIKey: VSRRLIKKZGFAMN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 601.13, ALogP 7.02, HBA 9, HBD 2, PSA 83.37, QED 0.19
Compound (SMILES): CC(C)n1c(Nc2ccc(NC(=O)Nc3ccc(F)c(Cl)c3)cc2)nc2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc21
InChIKey: OAZZXYMTTQCAGN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 629.14, ALogP 7.08, HBA 9, HBD 4, PSA 115.27, QED 0.14
Compound (SMILES): CC(C)n1c(Nc2ccc(C(=O)Nc3cccc(F)c3)cc2)nc2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc21
InChIKey: IKULNRLYMKMRGA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 579.68, ALogP 6.04, HBA 9, HBD 3, PSA 103.24, QED 0.2
Compound (SMILES): CC(C)n1c(Nc2ccc(C(F)(F)F)cc2)nc2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc21
InChIKey: FSMLLEGNJUYKOD-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 510.57, ALogP 5.67, HBA 8, HBD 2, PSA 74.14, QED 0.35
Compound (SMILES): CC(C)n1c(Nc2cccnc2)nc2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc21
InChIKey: WSOHOUHPUOAXIN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 443.56, ALogP 4.04, HBA 9, HBD 2, PSA 87.03, QED 0.46
Compound (SMILES): CC(C)n1c(NC2CCCCC2)nc2cnc(Nc3ccc(N4CCN(C)CC4)cc3)nc21
InChIKey: IDRLVNWZKKHTGY-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 448.62, ALogP 4.65, HBA 8, HBD 2, PSA 74.14, QED 0.57
Compound (SMILES): C=CC(=O)Nc1cccc(Nc2ncc3nc(Nc4ccccc4)n(C(C)C)c3n2)c1
InChIKey: KJFSEEWSSQIOAL-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition Assay: The object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro. In this assay, an isotopic labeling method was used to label the gamma phosphate group on ATP. EGFR (including wild type, L858R mutant type and L858R/T790M double mutant type), VEGFR2, ALK, BTK, c-KIT, c-SRC, MET, PDGFRalpha and FLT3 kinases were tested in vitro for the activity inhibition. Staurosporine was used as a reference molecule (or referred to as a positive control). The kinase inhibitory activities of the tested compounds were expressed in the IC50 value (half inhibition concentration) or the kinase activity inhibitory rate by the tested compounds at 10 uM. The IC50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds. 1. Materials:  20mM 3-(N-morpholinyl)propylsulfonic acid (MOPS);  1mM Ethylenediaminetetraacetic acid (EDTA);  0.01% Polyethylene glycol lauryl ether (Brij-35).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 413.49, ALogP 5.02, HBA 7, HBD 3, PSA 96.76, QED 0.37
Compound (SMILES): CO[C@]12CC[C@@]3(C[C@@H]1COCc1ccc(F)cc1)[C@H]1Cc4ccc(O)c5c4[C@@]3(CC[N+]1(C)CC1CC1)[C@H]2O5
InChIKey: KDRPLPCXUIBXLY-SWNZWMJTSA-O
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Membranes from recombinant HEK-293 cells expressing the human kippa opioid receptor (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4 C. and pellets were resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of kippa receptor membranes were stored at -80 C.Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 ug membrane protein (recombinant K opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 ul binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4).
Measurement: Ki = 0.26 nM (pChEMBL 9.59000015258789)
Descriptors: MW 520.67, ALogP 5.12, HBA 4, HBD 1, PSA 47.92, QED 0.52
Compound (SMILES): CO[C@]12CC[C@@]3(C[C@@H]1COCc1cc4ccccc4s1)[C@H]1Cc4ccc(O)c5c4[C@@]3(CC[N+]1(C)CC1CC1)[C@H]2O5
InChIKey: FSWJTBGGRGOWRE-PFNHLVLRSA-O
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Membranes from recombinant HEK-293 cells expressing the human kippa opioid receptor (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4 C. and pellets were resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of kippa receptor membranes were stored at -80 C.Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 ug membrane protein (recombinant K opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 ul binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4).
Measurement: Ki = 0.78 nM (pChEMBL 9.109999656677246)
Descriptors: MW 558.76, ALogP 6.19, HBA 5, HBD 1, PSA 47.92, QED 0.35
Compound (SMILES): CO[C@]12CC[C@@]3(C[C@@H]1COCc1ccc(C)cc1)[C@H]1Cc4ccc(O)c5c4[C@@]3(CC[N+]1(C)CC1CC1)[C@H]2O5
InChIKey: IGOLICYRRBXJAC-QAKVHLFHSA-O
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Membranes from recombinant HEK-293 cells expressing the human kippa opioid receptor (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4 C. and pellets were resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of kippa receptor membranes were stored at -80 C.Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 ug membrane protein (recombinant K opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 ul binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4).
Measurement: Ki = 1.06 nM (pChEMBL 8.970000267028809)
Descriptors: MW 516.7, ALogP 5.29, HBA 4, HBD 1, PSA 47.92, QED 0.51
Compound (SMILES): CO[C@]12CC[C@@]3(C[C@@H]1COCc1ccccc1)[C@H]1Cc4ccc(O)c5c4[C@@]3(CC[N+]1(C)CC1CC1)[C@H]2O5
InChIKey: TTXDZHRSIOJYMD-YDVXKPGUSA-O
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Membranes from recombinant HEK-293 cells expressing the human kippa opioid receptor (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4 C. and pellets were resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of kippa receptor membranes were stored at -80 C.Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 ug membrane protein (recombinant K opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 ul binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4).
Measurement: Ki = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 502.68, ALogP 4.98, HBA 4, HBD 1, PSA 47.92, QED 0.54
Compound (SMILES): COc1ccc(COC[C@H]2C[C@@]34CC[C@]2(OC)[C@@H]2Oc5c(OC)ccc6c5[C@@]23CC[N+](C)(CC2CC2)[C@@H]4C6)cc1
InChIKey: RACAYAPCAUMASR-GQOOHXPWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Membranes from recombinant HEK-293 cells expressing the human kippa opioid receptor (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4 C. and pellets were resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of kippa receptor membranes were stored at -80 C.Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 ug membrane protein (recombinant K opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 ul binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4).
Measurement: Ki = 56.98 nM (pChEMBL 7.239999771118164)
Descriptors: MW 546.73, ALogP 5.29, HBA 5, HBD 0, PSA 46.15, QED 0.4
Compound (SMILES): CO[C@]12CC[C@@]3(C[C@@H]1COCc1ccoc1)[C@H]1Cc4ccc(O)c5c4[C@@]3(CC[N+]1(C)CC1CC1)[C@H]2O5
InChIKey: VTGIBPDRGIZMNY-OKFFUYMDSA-O
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Membranes from recombinant HEK-293 cells expressing the human kippa opioid receptor (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4 C. and pellets were resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of kippa receptor membranes were stored at -80 C.Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 ug membrane protein (recombinant K opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 ul binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4).
Measurement: Ki = 0.29 nM (pChEMBL 9.539999961853027)
Descriptors: MW 492.64, ALogP 4.57, HBA 5, HBD 1, PSA 61.06, QED 0.57
Compound (SMILES): CO[C@]12CC[C@@]3(C[C@@H]1COCc1ccsc1)[C@H]1Cc4ccc(O)c5c4[C@@]3(CC[N+]1(C)CC1CC1)[C@H]2O5
InChIKey: MRDMZRJKFOWUTI-OKFFUYMDSA-O
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Membranes from recombinant HEK-293 cells expressing the human kippa opioid receptor (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4 C. and pellets were resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of kippa receptor membranes were stored at -80 C.Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 ug membrane protein (recombinant K opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 ul binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4).
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 508.7, ALogP 5.04, HBA 5, HBD 1, PSA 47.92, QED 0.53
Compound (SMILES): CO[C@]12CC[C@@]3(C[C@@H]1COCc1ccccc1F)[C@H]1Cc4ccc(O)c5c4[C@@]3(CC[N+]1(C)CC1CC1)[C@H]2O5
InChIKey: TTZUHMSWPUSRCD-SWNZWMJTSA-O
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Membranes from recombinant HEK-293 cells expressing the human kippa opioid receptor (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4 C. and pellets were resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of kippa receptor membranes were stored at -80 C.Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 ug membrane protein (recombinant K opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 ul binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4).
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 520.67, ALogP 5.12, HBA 4, HBD 1, PSA 47.92, QED 0.52
Compound (SMILES): CO[C@]12CC[C@@]3(C[C@@H]1COCc1cccc(C)c1)[C@H]1Cc4ccc(O)c5c4[C@@]3(CC[N+]1(C)CC1CC1)[C@H]2O5
InChIKey: AKPVGOXFKIVLEA-QAKVHLFHSA-O
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Membranes from recombinant HEK-293 cells expressing the human kippa opioid receptor (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4 C. and pellets were resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of kippa receptor membranes were stored at -80 C.Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 ug membrane protein (recombinant K opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 ul binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4).
Measurement: Ki = 0.29 nM (pChEMBL 9.539999961853027)
Descriptors: MW 516.7, ALogP 5.29, HBA 4, HBD 1, PSA 47.92, QED 0.51
Compound (SMILES): CO[C@]12CC[C@@]3(C[C@@H]1COCc1cccc(F)c1)[C@H]1Cc4ccc(O)c5c4[C@@]3(CC[N+]1(C)CC1CC1)[C@H]2O5
InChIKey: BPIBUZITIQNJJE-SWNZWMJTSA-O
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Membranes from recombinant HEK-293 cells expressing the human kippa opioid receptor (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4 C. and pellets were resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of kippa receptor membranes were stored at -80 C.Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 ug membrane protein (recombinant K opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 ul binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4).
Measurement: Ki = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 520.67, ALogP 5.12, HBA 4, HBD 1, PSA 47.92, QED 0.52
Compound (SMILES): CO[C@]12CC[C@@]3(C[C@@H]1COCc1cccc(Cl)c1)[C@H]1Cc4ccc(O)c5c4[C@@]3(CC[N+]1(C)CC1CC1)[C@H]2O5
InChIKey: ORDXGIVMEUSTMZ-SWNZWMJTSA-O
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Membranes from recombinant HEK-293 cells expressing the human kippa opioid receptor (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000xg for 15 min at 4 C. and pellets were resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of kippa receptor membranes were stored at -80 C.Radioligand dose displacement assays used 0.4 nM [3H]-U69,593 (GE Healthcare, Piscataway, N.J.; 40 Ci/mmole) with 15 ug membrane protein (recombinant K opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 ul binding buffer (5% DMSO, 50 mM Trizma base, pH 7.4).
Measurement: Ki = 0.27 nM (pChEMBL 9.569999694824219)
Descriptors: MW 537.12, ALogP 5.63, HBA 4, HBD 1, PSA 47.92, QED 0.47
Compound (SMILES): O=C(NCC1(c2ccc(F)nc2)CCC(F)(F)CC1)c1ccccc1F
InChIKey: DJWHQZRHGSJBCB-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Binding Assay: Fluorescent Imaging Plate Reader (FLIPR) assay: Briefly, 293-human or mouse P2X7 stable cells were incubated in sucrose buffer, pH 7.4 [KCl (5 mM), NaH2PO4.2H2O (9.6 mM), HEPES (25 mM), sucrose (280 mM), glucose (5 mM), CaCl2 (0.5 mM), and probenecid (0.1425 g in 3 mL 1N NaOH was added for 500 mL solution)] in 384-well plates.293-rat P2X7 stable cells were incubated in HHPB (pH 7.4) [consisting of Hank's BSS (1×); HEPES (pH 7.4) (20 mM) (Sigma); probenecid (0.710g/5 mL 1N NaOH) (Sigma); and BSA (0.05%) (Roche) which was added after the pH had been adjusted] in 384-well plates. Fluo-4 NW dye mix (Molecular Probes, Inc., Eugene, Oreg., USA) was prepared in buffer (see manufacturer's instructions). Cell plates were removed from the 37° C. incubator, the media discarded and then 30 μL of dye was added to each well. Plates were placed in the 37° C., non-CO2 incubator for 30 minutes and then room temperature for 30 minutes.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 366.36, ALogP 4.24, HBA 2, HBD 1, PSA 41.99, QED 0.65
Compound (SMILES): O=C(NCC(CC1CC1)c1ccc(C(F)(F)F)nc1)c1cccc(Cl)c1Cl
InChIKey: FJZHHXCQDLYUDX-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Binding Assay: Fluorescent Imaging Plate Reader (FLIPR) assay: Briefly, 293-human or mouse P2X7 stable cells were incubated in sucrose buffer, pH 7.4 [KCl (5 mM), NaH2PO4.2H2O (9.6 mM), HEPES (25 mM), sucrose (280 mM), glucose (5 mM), CaCl2 (0.5 mM), and probenecid (0.1425 g in 3 mL 1N NaOH was added for 500 mL solution)] in 384-well plates.293-rat P2X7 stable cells were incubated in HHPB (pH 7.4) [consisting of Hank's BSS (1×); HEPES (pH 7.4) (20 mM) (Sigma); probenecid (0.710g/5 mL 1N NaOH) (Sigma); and BSA (0.05%) (Roche) which was added after the pH had been adjusted] in 384-well plates. Fluo-4 NW dye mix (Molecular Probes, Inc., Eugene, Oreg., USA) was prepared in buffer (see manufacturer's instructions). Cell plates were removed from the 37° C. incubator, the media discarded and then 30 μL of dye was added to each well. Plates were placed in the 37° C., non-CO2 incubator for 30 minutes and then room temperature for 30 minutes.
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 417.26, ALogP 5.72, HBA 2, HBD 1, PSA 41.99, QED 0.65
Compound (SMILES): O=C(NCC(CC1CC1)c1ccc(C(F)(F)F)nc1)c1ccccc1Cl
InChIKey: KHWQIZKQWLPKRO-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Binding Assay: Fluorescent Imaging Plate Reader (FLIPR) assay: Briefly, 293-human or mouse P2X7 stable cells were incubated in sucrose buffer, pH 7.4 [KCl (5 mM), NaH2PO4.2H2O (9.6 mM), HEPES (25 mM), sucrose (280 mM), glucose (5 mM), CaCl2 (0.5 mM), and probenecid (0.1425 g in 3 mL 1N NaOH was added for 500 mL solution)] in 384-well plates.293-rat P2X7 stable cells were incubated in HHPB (pH 7.4) [consisting of Hank's BSS (1×); HEPES (pH 7.4) (20 mM) (Sigma); probenecid (0.710g/5 mL 1N NaOH) (Sigma); and BSA (0.05%) (Roche) which was added after the pH had been adjusted] in 384-well plates. Fluo-4 NW dye mix (Molecular Probes, Inc., Eugene, Oreg., USA) was prepared in buffer (see manufacturer's instructions). Cell plates were removed from the 37° C. incubator, the media discarded and then 30 μL of dye was added to each well. Plates were placed in the 37° C., non-CO2 incubator for 30 minutes and then room temperature for 30 minutes.
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 382.81, ALogP 5.07, HBA 2, HBD 1, PSA 41.99, QED 0.76
Compound (SMILES): Cc1ncc(C(CNC(=O)c2cccc(Cl)c2Cl)CC2(C(F)(F)F)CC2)cn1
InChIKey: SVXAGFVIOFXJNP-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Binding Assay: Fluorescent Imaging Plate Reader (FLIPR) assay: Briefly, 293-human or mouse P2X7 stable cells were incubated in sucrose buffer, pH 7.4 [KCl (5 mM), NaH2PO4.2H2O (9.6 mM), HEPES (25 mM), sucrose (280 mM), glucose (5 mM), CaCl2 (0.5 mM), and probenecid (0.1425 g in 3 mL 1N NaOH was added for 500 mL solution)] in 384-well plates.293-rat P2X7 stable cells were incubated in HHPB (pH 7.4) [consisting of Hank's BSS (1×); HEPES (pH 7.4) (20 mM) (Sigma); probenecid (0.710g/5 mL 1N NaOH) (Sigma); and BSA (0.05%) (Roche) which was added after the pH had been adjusted] in 384-well plates. Fluo-4 NW dye mix (Molecular Probes, Inc., Eugene, Oreg., USA) was prepared in buffer (see manufacturer's instructions). Cell plates were removed from the 37° C. incubator, the media discarded and then 30 μL of dye was added to each well. Plates were placed in the 37° C., non-CO2 incubator for 30 minutes and then room temperature for 30 minutes.
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 432.27, ALogP 5.34, HBA 3, HBD 1, PSA 54.88, QED 0.67