lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C=C[C@@H]1C[C@]1(NC(=O)[C@@H]1C[C@@]2(CN1C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCCN1C(C)C)C1CCCCC1)C(C)(C)C)C(C)(C)C21CCC1)C(=O)NS(=O)(=O)N(C)C
InChIKey: LOYIQGBTNJFCIL-ZPWJQIKTSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 1a (isolate H) (HCV)
UniProt: P27958
Assay: Protease Assay: The inhibitory activity of certain compounds of Table A against HCV NS3-4A serine protease is determined in a homogenous assay using the full-length NS3-4A protein (genotype 1a, strain HCV-1) and a commercially available internally-quenched fluorogenic peptide substrate as described by Taliani, M., et al. 1996 Anal. Biochem. 240:60-67, which is incorporated by reference in its entirety.
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 830.15, ALogP 3.63, HBA 8, HBD 4, PSA 177.33, QED 0.2
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(=O)(=O)C3CC3)cc2)ncc1C(F)(F)F
InChIKey: BAOWDLOLYGOWOE-GHMZBOCLSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: VEGF receptor tyrosine kinase (90 ng/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 M) in 30 ul of assay buffer [40 mM Tris/HCl pH 5.5; 10 mM MgCl2; 1 mM MnCl2; 3 uM Na ortho-vanadate; 1.0 mM dithiothreitol; 8 uM adenosine trisphosphate (ATP); 0.96 ug/measuring point poly-(Glu4Tyr); 0.2 uCi/measuring point 33P-gamma ATP; 1.4% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C.
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 431.44, ALogP 3.32, HBA 7, HBD 2, PSA 101.41, QED 0.69
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc(S(C)(=O)=O)cc2)ncc1C(F)(F)F
InChIKey: JLMIHNJHBAEFKC-NXEZZACHSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: VEGF receptor tyrosine kinase (90 ng/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 M) in 30 ul of assay buffer [40 mM Tris/HCl pH 5.5; 10 mM MgCl2; 1 mM MnCl2; 3 uM Na ortho-vanadate; 1.0 mM dithiothreitol; 8 uM adenosine trisphosphate (ATP); 0.96 ug/measuring point poly-(Glu4Tyr); 0.2 uCi/measuring point 33P-gamma ATP; 1.4% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C.
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 405.4, ALogP 2.79, HBA 7, HBD 2, PSA 101.41, QED 0.76
Compound (SMILES): C[C@@H](Oc1nc(Nc2ccc(S(C)(=O)=O)cc2)ncc1C(F)(F)F)C(C)(C)O
InChIKey: PAEDTQQTYBULPN-SNVBAGLBSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: VEGF receptor tyrosine kinase (90 ng/measuring point) was incubated for 10 min at 22 C. in the presence of different concentrations of test substances (0 uM, and within the range 0.001-10 M) in 30 ul of assay buffer [40 mM Tris/HCl pH 5.5; 10 mM MgCl2; 1 mM MnCl2; 3 uM Na ortho-vanadate; 1.0 mM dithiothreitol; 8 uM adenosine trisphosphate (ATP); 0.96 ug/measuring point poly-(Glu4Tyr); 0.2 uCi/measuring point 33P-gamma ATP; 1.4% dimethyl sulphoxide]. The reaction was stopped by adding EDTA solution (250 mM; pH 8.0; 15 ul/measuring point).From each reaction mixture, 15 ul were applied to P30 filter strips (Wallac), and unincorporated 33P-ATP was removed by washing the filter strips three times, for 10 min in each case, in 0.5% phosphoric acid. After drying the filter strips for 1 hour at 70 C., the filter strips were covered with scintillator strips (MeltiLex A, Wallac) and stoved for 1 hour at 90 C.
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 419.43, ALogP 3.18, HBA 7, HBD 2, PSA 101.41, QED 0.74
Compound (SMILES): CC(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: PWVBXAIRJXQMCU-VEEPYNQNSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Competitive Inhibition Assay: A competitive inhibition binding assay is performed using membrane homogenates prepared from HEK-293 cells that express recombinant hMC4-R, hMC3-R, or hMC5-R, and from B-16 mouse melanoma cells (containing endogenous MC1-R). In some instances, HEK-293 cells that express recombinant hMC1-R were employed. In the examples that follow, all MC3-R, MC4-R and MC5-R values are for human recombinant receptors. MC1-R values are for B-16 mouse melanoma cells, unless the heading is hMC1-R, in which case the value is for human recombinant MC1-R. Assays were performed in 96 well GF/B Millipore multiscreen filtration plates (MAFB NOB10) pre-coated with 0.5% bovine serum albumin (Fraction V). Membrane homogenates were incubated with 0.2 nM (for hMC4-R) 0.4 nM (for MC3-R and MC5-R) or 0.1 nM (for mouse B16 MC1-R or hMC1-R) [I125]-NDP-alpha -MSH (Perkin Elmer) and increasing concentrations of test peptides of the present invention in buffer containing 25 mM HEPES buffer (pH 7.5) with 100 mM NaCl.
Measurement: Ki = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 1058.22
Compound (SMILES): COc1cccc(C2=NCC(=O)N3CCc4c(OC)cccc4C3=C2)c1
InChIKey: PJHSICZFRHXHMB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 348.4, ALogP 2.93, HBA 4, HBD 0, PSA 51.13, QED 0.86
Compound (SMILES): COCc1cn(C2=NCC(=O)N3CCc4c(cccc4C4CC4)C3=C2)cn1
InChIKey: MBZUZSSPUFLUTF-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Fluorometric Imaging Plate Reader (FLIPR) Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk-) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996). Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 362.43, ALogP 2.59, HBA 5, HBD 0, PSA 59.72, QED 0.84
Compound (SMILES): CCn1c(=O)c2cnc3c(Cl)cccc3c2n(C2CCCC2)c1=O
InChIKey: RNTPXDNXVJTNNP-UHFFFAOYSA-N
Target: Lipopolysaccharide-induced tumor necrosis factor-alpha factor (SINGLE PROTEIN), Homo sapiens
UniProt: Q99732
Assay: TNF inhibition assay: Samples were tested for TNF as per the manufacturer's instructions (TNF ELISA; R&D Systems, Cat #DY210). The samples were serially diluted with PBS+1% BSA to the appropriate dilution condition for the cell prep, typically a 1:4 or 1:6 dilution.
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 343.81, ALogP 3.5, HBA 5, HBD 0, PSA 56.89, QED 0.67
Compound (SMILES): CCCc1cccc2c1ncc1c(=O)n(CC)c(=O)n(C3CCCC3)c12
InChIKey: IAIFPELWEXGBKC-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 351.45, ALogP 3.8, HBA 5, HBD 0, PSA 56.89, QED 0.67
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3ccc4c(c3)OCO4)c(=O)n(C3CCCC3)c12
InChIKey: JMKXHWHMULJLQG-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 513 nM (pChEMBL 6.289999961853027)
Descriptors: MW 431.45, ALogP 3.55, HBA 8, HBD 0, PSA 84.58, QED 0.46
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3cccc(Cl)c3)c(=O)n(C3CCN(S(C)(=O)=O)CC3)c12
InChIKey: MUQKVPSLHRVESB-UHFFFAOYSA-N
Target: Lipopolysaccharide-induced tumor necrosis factor-alpha factor (SINGLE PROTEIN), Homo sapiens
UniProt: Q99732
Assay: TNF inhibition assay: Samples were tested for TNF as per the manufacturer's instructions (TNF ELISA; R&D Systems, Cat #DY210). The samples were serially diluted with PBS+1% BSA to the appropriate dilution condition for the cell prep, typically a 1:4 or 1:6 dilution.
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 514.99, ALogP 2.96, HBA 8, HBD 0, PSA 103.5, QED 0.39
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3cccc(Cl)c3)c(=O)n([C@H]3CCN(S(C)(=O)=O)C3)c12
InChIKey: QBTZSDNOQVLDBB-INIZCTEOSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 206 nM (pChEMBL 6.690000057220459)
Descriptors: MW 500.96, ALogP 2.57, HBA 8, HBD 0, PSA 103.5, QED 0.4
Compound (SMILES): O=C(Nc1ccc(N2CCc3ccncc3C2)cc1)c1cccc(C(F)(F)F)c1
InChIKey: GPILFGJABMRGLK-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRβ kinase assays were performed in 96 well microliter plates that were coated overnight with 75 μg of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 μL reaction volumes containing 36 μM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30° C., the reactions were washed 2 mls per well PBS-T. 100 μl of a monoclonal anti-phosphotyrosine antibody-peroxidase conjugate diluted 1:10,000 in PBS-T was added to the wells for 30 minutes. Following a 2 mls per well wash with PBS-Tween-20, 100 μl of O-Phenylenediamine Dihydrochloride in phosphate-citrate buffer, containing urea hydrogen peroxide, was added to the wells for 7-10 minutes as a colorimetric substrate for the peroxidase. The reaction was terminated by the addition of 100 μl of 2.5N H2SO4 to each well and read using a microplate ELISA reader set at 492 nm.
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 397.4, ALogP 4.92, HBA 3, HBD 1, PSA 45.23, QED 0.68
Compound (SMILES): Cc1cccc(NC(=O)Nc2ccc(N3CCc4ccncc4C3)cc2)c1
InChIKey: QBEDAVXOZVBLMC-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRβ kinase assays were performed in 96 well microliter plates that were coated overnight with 75 μg of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 μL reaction volumes containing 36 μM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30° C., the reactions were washed 2 mls per well PBS-T. 100 μl of a monoclonal anti-phosphotyrosine antibody-peroxidase conjugate diluted 1:10,000 in PBS-T was added to the wells for 30 minutes. Following a 2 mls per well wash with PBS-Tween-20, 100 μl of O-Phenylenediamine Dihydrochloride in phosphate-citrate buffer, containing urea hydrogen peroxide, was added to the wells for 7-10 minutes as a colorimetric substrate for the peroxidase. The reaction was terminated by the addition of 100 μl of 2.5N H2SO4 to each well and read using a microplate ELISA reader set at 492 nm.
Measurement: Ki = 1560 nM (pChEMBL 5.809999942779541)
Descriptors: MW 358.45, ALogP 4.6, HBA 3, HBD 2, PSA 57.26, QED 0.72
Compound (SMILES): O=C(Nc1ccccc1)Nc1ccc(N2CCc3ccncc3C2)cc1
InChIKey: DETQEUBCKFGKNU-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFR.beta. kinase assays were performed in 96 well microtiter plates that were coated overnight with 75 .mu.g of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mLs per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mLs per well PBS-T prior to starting the reaction. Reactions were carried out in 100 .mu.L reaction volumes containing 36 .mu.M ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl.sub.2, 0.1 mM MnCl.sub.2 and 0.2 mM Na.sub.3VO.sub.4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 344.42, ALogP 4.29, HBA 3, HBD 2, PSA 57.26, QED 0.75
Compound (SMILES): Cc1ccc(NC(=O)Nc2ccc(N3CCc4ccncc4C3)cc2)cc1
InChIKey: SFNSIRBXKCUTMM-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRβ kinase assays were performed in 96 well microliter plates that were coated overnight with 75 μg of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 μL reaction volumes containing 36 μM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30° C., the reactions were washed 2 mls per well PBS-T. 100 μl of a monoclonal anti-phosphotyrosine antibody-peroxidase conjugate diluted 1:10,000 in PBS-T was added to the wells for 30 minutes. Following a 2 mls per well wash with PBS-Tween-20, 100 μl of O-Phenylenediamine Dihydrochloride in phosphate-citrate buffer, containing urea hydrogen peroxide, was added to the wells for 7-10 minutes as a colorimetric substrate for the peroxidase. The reaction was terminated by the addition of 100 μl of 2.5N H2SO4 to each well and read using a microplate ELISA reader set at 492 nm.
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 358.45, ALogP 4.6, HBA 3, HBD 2, PSA 57.26, QED 0.72
Compound (SMILES): Cc1cccc(NC(=O)Nc2ccc(N3CCc4ccncc4C3)c(C)c2)c1
InChIKey: HMQWFQHVYCBHFE-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRβ kinase assays were performed in 96 well microliter plates that were coated overnight with 75 μg of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 μL reaction volumes containing 36 μM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30° C., the reactions were washed 2 mls per well PBS-T. 100 μl of a monoclonal anti-phosphotyrosine antibody-peroxidase conjugate diluted 1:10,000 in PBS-T was added to the wells for 30 minutes. Following a 2 mls per well wash with PBS-Tween-20, 100 μl of O-Phenylenediamine Dihydrochloride in phosphate-citrate buffer, containing urea hydrogen peroxide, was added to the wells for 7-10 minutes as a colorimetric substrate for the peroxidase. The reaction was terminated by the addition of 100 μl of 2.5N H2SO4 to each well and read using a microplate ELISA reader set at 492 nm.
Measurement: Ki = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 372.47, ALogP 4.91, HBA 3, HBD 2, PSA 57.26, QED 0.69
Compound (SMILES): Cc1cccc(NC(=O)Nc2ccc(N3CCc4ccncc4C3)cc2C)c1
InChIKey: IGDCJUNQEHDNIA-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRβ kinase assays were performed in 96 well microliter plates that were coated overnight with 75 μg of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 μL reaction volumes containing 36 μM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30° C., the reactions were washed 2 mls per well PBS-T. 100 μl of a monoclonal anti-phosphotyrosine antibody-peroxidase conjugate diluted 1:10,000 in PBS-T was added to the wells for 30 minutes. Following a 2 mls per well wash with PBS-Tween-20, 100 μl of O-Phenylenediamine Dihydrochloride in phosphate-citrate buffer, containing urea hydrogen peroxide, was added to the wells for 7-10 minutes as a colorimetric substrate for the peroxidase. The reaction was terminated by the addition of 100 μl of 2.5N H2SO4 to each well and read using a microplate ELISA reader set at 492 nm.
Measurement: Ki = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 372.47, ALogP 4.91, HBA 3, HBD 2, PSA 57.26, QED 0.69
Compound (SMILES): CC(C)c1cccc(NC(=O)c2cccc(N3CCc4ccncc4C3)c2)c1
InChIKey: RHNRCAGSWLRFCY-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRβ kinase assays were performed in 96 well microliter plates that were coated overnight with 75 μg of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 μL reaction volumes containing 36 μM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30° C., the reactions were washed 2 mls per well PBS-T. 100 μl of a monoclonal anti-phosphotyrosine antibody-peroxidase conjugate diluted 1:10,000 in PBS-T was added to the wells for 30 minutes. Following a 2 mls per well wash with PBS-Tween-20, 100 μl of O-Phenylenediamine Dihydrochloride in phosphate-citrate buffer, containing urea hydrogen peroxide, was added to the wells for 7-10 minutes as a colorimetric substrate for the peroxidase. The reaction was terminated by the addition of 100 μl of 2.5N H2SO4 to each well and read using a microplate ELISA reader set at 492 nm.
Measurement: Ki = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 371.48, ALogP 5.02, HBA 3, HBD 1, PSA 45.23, QED 0.7
Compound (SMILES): COC(=O)c1cncc2c1CCN(c1cccc(C(=O)Nc3cccc(C(C)C)c3)c1)C2
InChIKey: HTJCJGPUYPCIIH-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRβ kinase assays were performed in 96 well microliter plates that were coated overnight with 75 μg of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 μL reaction volumes containing 36 μM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30° C., the reactions were washed 2 mls per well PBS-T. 100 μl of a monoclonal anti-phosphotyrosine antibody-peroxidase conjugate diluted 1:10,000 in PBS-T was added to the wells for 30 minutes. Following a 2 mls per well wash with PBS-Tween-20, 100 μl of O-Phenylenediamine Dihydrochloride in phosphate-citrate buffer, containing urea hydrogen peroxide, was added to the wells for 7-10 minutes as a colorimetric substrate for the peroxidase. The reaction was terminated by the addition of 100 μl of 2.5N H2SO4 to each well and read using a microplate ELISA reader set at 492 nm.
Measurement: Ki = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 429.52, ALogP 4.81, HBA 5, HBD 1, PSA 71.53, QED 0.59
Compound (SMILES): Nc1ncc2c(n1)CCN(c1cccc(C(=O)Nc3ccc(F)c(C(F)(F)F)c3)c1)C2
InChIKey: QSZWCFNHVHQHSX-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRβ kinase assays were performed in 96 well microliter plates that were coated overnight with 75 μg of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 μL reaction volumes containing 36 μM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30° C., the reactions were washed 2 mls per well PBS-T. 100 μl of a monoclonal anti-phosphotyrosine antibody-peroxidase conjugate diluted 1:10,000 in PBS-T was added to the wells for 30 minutes. Following a 2 mls per well wash with PBS-Tween-20, 100 μl of O-Phenylenediamine Dihydrochloride in phosphate-citrate buffer, containing urea hydrogen peroxide, was added to the wells for 7-10 minutes as a colorimetric substrate for the peroxidase. The reaction was terminated by the addition of 100 μl of 2.5N H2SO4 to each well and read using a microplate ELISA reader set at 492 nm.
Measurement: Ki = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 431.39, ALogP 4.03, HBA 5, HBD 2, PSA 84.14, QED 0.61
Compound (SMILES): O=c1[nH]nc2c3c(cccc13)N=C(CN1Cc3ccccc3C1)N2
InChIKey: JLFSBHQQXIAQEC-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of human recombinant TNKS1 by chemiluminescent assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 317.35, ALogP 2.39, HBA 5, HBD 2, PSA 73.38, QED 0.76
Compound (SMILES): Nc1ncnc2c1ncn2[C@H]1O[C@@H](CN(CCNCCc2ccc(Cl)cc2)CC[C@H](N)C(=O)O)[C@H](O)[C@@H]1O
InChIKey: WWKSYRSOVZNFOY-HMDXBLRFSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Compound 75 was serially diluted 3 fold in DMSO for 10 points and 1 μL was plated in a 384 well microtiter plate. Positive control (100% inhibition standard) was 100 μM final concentration of SAH and negative control (0% inhibition standard) contained 1 μL of DMSO. Compound 75 was then incubated for 30 minutes with 40 μL per well of EZH2 wild-type and mutants at 8 nM in pH 7.6 assay buffer (20 mM BICINE, 100 mM KCl, 1 mM DTT, 0.002% Tween 20, 0.005% BSG). A substrate mix at 10 μL per well was added which contained 5-adenosylmethionine-Cl (SAM) at 150 nM and tritiated SAM at 100 nM, and biotinylated oligonucleosome at 150 nM in pH 7.6 assay buffer. Quenched enzyme reaction was transferred to a streptavidin-coated Flashplate (Perkin Elmer, catalog number SMP410), allowed to bind for one hour, and detected on a TopCount NXT HTS (Perkin Elmer).
Measurement: IC50 = 7180 nM (pChEMBL 5.139999866485596)
Descriptors: MW 549.03, ALogP -0.38, HBA 12, HBD 6, PSA 197.9, QED 0.15
Compound (SMILES): CCc1cc(O)c(F)cc1-c1ccc2c(-c3nc4c([nH]3)CCN(C(=O)c3ccc(F)cc3)C4)n[nH]c2c1
InChIKey: SYMXGYXFLGDULR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST tagged human recombinant JAK2 catalytic domain expressed in baculovirus using peptide substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by microfluidic assay
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 499.52, ALogP 5.36, HBA 4, HBD 3, PSA 97.9, QED 0.31
Compound (SMILES): CCc1cc(O)c(F)cc1-c1ccc2c(-c3nc4c([nH]3)CCN(C(=O)c3ccsn3)C4)n[nH]c2c1
InChIKey: NZXZOMXHKCFGLS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: High ATP Caliper Endpoint Assay: JAK1 enzyme (Invitrogen) stock solution is made up at 5.2 uM in sterile water. JAK1 enzyme stock is diluted to 20 nM in assay buffer (10 mM HEPES free acid pH 7.5, 10 mM HEPES free base pH 7.5, 10 mM MgCL2, 0.0005% Tween-20, 0.01% BSA) containing 2 mM DTT (all supplied by Sigma) with the addition of one protease tablet per 25 mls buffer (Roche). ATP is made up at 10 mM stock in sterile water and diluted to 5 mM in assay buffer. Peptide H236 (Caliper Life Sciences) is made up at 1.5 mM in 100% DMSO and diluted to 3 uM in assay buffer. Stop buffer comprises 140 mM HEPES, 22.5 mM EDTA (Sigma) and 0.15% coating reagent (Caliper Life Sciences).Assays are performed in Greiner polypropylene 384 well plates. Following compound preparation within the plate 10 ul of enzyme in assay buffer containing DTT is added using a Multidrop Micro. Final assay concentration of enzyme is 10 nM. Compound and enzyme are pre-incubated for 30 minutes at room temperature.
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 488.55, ALogP 4.68, HBA 6, HBD 3, PSA 110.79, QED 0.34
Compound (SMILES): CCc1cc(O)c(F)cc1-c1ccc2c(-c3nc4c([nH]3)CCN(C(=O)c3cnc(N5CCCCC5)cn3)C4)n[nH]c2c1
InChIKey: XDJGNPSZQSWJCV-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of Tyk2 (unknown origin) using peptide substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by microfluidic assay
Measurement: IC50 = 29.7 nM (pChEMBL 7.53000020980835)
Descriptors: MW 566.64, ALogP 5.01, HBA 7, HBD 3, PSA 126.92, QED 0.27
Compound (SMILES): CC(=O)N[C@@H](C)COc1ccc(Oc2ccc(OC(C)C)cc2)cc1
InChIKey: YIZVHILZJRFUOV-HNNXBMFYSA-N
Target: Acetyl-CoA carboxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O00763
Assay: Luminometric Assay: The reaction mixture contained 50 mM tris acetate (Merck, #1.08382.1000), pH 7.5, 250 μM acetyl coenzyme A (Sigma, #A2181),16 mM NaHCO3 (Merck, #1.06329.0500), 0.9 mg/ml bovine serum albumin (Sigma, #A8806), 25 μM ATP (Sigma, #A7699), 1.1 μM β-mercaptoethanol (Roth, #4227,1), 4.3 mM magnesium acetate ((Merck, #1.05819.0250), 10 mM sodium citrate (Merck, #1.06448.0500) and 200-400 ng of the ACC preparations. The mixture also contained a test compound. The test compounds were each dissolved in 10 mM DMSO and were assayed at final concentrations of 0 μM, 0.01 μM, 0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM, 10 μM, 30 μM and 100 μM. The final concentration of the DMSO in the assay was 0.1% (v/v). The reaction was started by adding ACC and was carried out at 37° C. for 90 min. The reaction was then stopped by adding 150 μl of 0.5 M tris acetate. 10 μl of the mixture were removed and mixed with 90 μl of ATP monitoring reagent (Cambrex, #LT27-002). After incubation for 10 min, the luminescence was measured in a luminometer (Tecan Genios Pro).
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 343.42, ALogP 4.17, HBA 4, HBD 1, PSA 56.79, QED 0.78
Compound (SMILES): CCOc1ccccc1-c1cccn2nc(Nc3ccc4c(c3)CCNCC4)nc12
InChIKey: LTPHZQBJCGYNFF-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: In Vitro Enzyme Assay: The ability of compounds to inhibit the kinase activity of baculovirus-expressed human FAK and JAK kinase using the time-resolved fluorescence (TRF) assay system.
Measurement: IC50 = 9999 nM (pChEMBL 5)
Descriptors: MW 399.5, ALogP 4.23, HBA 6, HBD 2, PSA 63.48, QED 0.53
Compound (SMILES): COCC(=O)N1CCN(c2ccc(Nc3ncc(C(N)=O)c(NC4CC4)n3)cc2)CC1
InChIKey: AKRODORBCFIPKJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Binding Assay: ATP-site dependent competition binding assay using Ambit KinomeScan Screening kit.
Measurement: Kd = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 425.49, ALogP 1.19, HBA 8, HBD 3, PSA 125.71, QED 0.58
Compound (SMILES): CS(=O)(=O)N1CCN(c2ccc(Nc3ncc(C(N)=O)c(NC4CC4)n3)cc2)CC1
InChIKey: PFDUPXGEXSITJW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Binding Assay: ATP-site dependent competition binding assay using Ambit KinomeScan Screening kit.
Measurement: Kd = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 431.52, ALogP 0.97, HBA 8, HBD 3, PSA 133.55, QED 0.59
Compound (SMILES): CCOC(=O)/C=C/c1c(OC)ccc2cc(-c3cccc(OC)c3)ccc12
InChIKey: WCLQUDCFQAVYPS-ACCUITESSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition Assay: Inhibition assay using P450 CYP enzymes.
Measurement: IC50 = 13400 nM (pChEMBL 4.869999885559082)
Descriptors: MW 362.43, ALogP 5.1, HBA 4, HBD 0, PSA 44.76, QED 0.45
Compound (SMILES): O=C(O)CCC(=O)Nc1ccc(-c2c(O)ccc3cc(-c4cccc(O)c4)ccc23)cc1
InChIKey: ZTMKPXUZAMIYCW-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37059
Assay: Radioactivity Assay: The determination of IC50 values was performed with enzyme isolated from human placenta (Luu-The, V. et al., J. Steroid Biochem. Mol. Biol., 55:581-587 (1995): Sam, K. M. et al., Drug Des Discov., 15:157-180 (1997)). The radioactivity is determined by means of scintillation measurement.
Measurement: IC50 = 1160 nM (pChEMBL 5.940000057220459)
Descriptors: MW 427.46, ALogP 5.39, HBA 4, HBD 4, PSA 106.86, QED 0.33
Compound (SMILES): CNC(=O)/C=C/c1cc(OC)cc(-c2ccc3cc(OC)ccc3c2)c1
InChIKey: VIZKFHFQFJRUES-RUDMXATFSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition Assay: Inhibition assay using P450 CYP enzymes.
Measurement: IC50 = 8830 nM (pChEMBL 5.050000190734863)
Descriptors: MW 347.41, ALogP 4.28, HBA 3, HBD 1, PSA 47.56, QED 0.7
Compound (SMILES): COc1ccc(Cn2c([C@@H](Cc3c[nH]c4ccccc34)NC(C)=O)nnc2[C@@H](Cc2c[nH]c3ccccc23)NC(=O)c2ccccn2)cc1
InChIKey: LDYITYSXTZVFHS-VSJLXWSYSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Competitive Binding Assay: Competitive binding assay using ghrelin receptor.
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 652.76, ALogP 5.83, HBA 7, HBD 4, PSA 142.61, QED 0.13
Compound (SMILES): COc1ccc(Cn2c([C@@H](Cc3ccccc3)NC(C)=O)nnc2[C@@H](Cc2c[nH]c3ccccc23)NC(=O)c2ccccn2)cc1
InChIKey: LFNRSBOROBEJIW-CZNDPXEESA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Competitive Binding Assay: Competitive binding assay using ghrelin receptor.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 613.72, ALogP 5.35, HBA 7, HBD 3, PSA 126.82, QED 0.17
Compound (SMILES): COc1ccc(Cn2c([C@@H](Cc3ccccc3)NC=O)nnc2[C@@H](Cc2c[nH]c3ccccc23)NC(=O)c2ccccn2)cc1
InChIKey: YSSONUCZBHLAKQ-ROJLCIKYSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Competitive Binding Assay: Competitive binding assay using ghrelin receptor.
Measurement: IC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 599.7, ALogP 4.95, HBA 7, HBD 3, PSA 126.82, QED 0.16
Compound (SMILES): COc1ccc(Cn2c([C@@H](Cc3ccccc3)NC(C)=O)nnc2[C@@H](Cc2c[nH]c3ccccc23)NC(=O)CO)cc1
InChIKey: HQOQKRHTKLWNAZ-FQLXRVMXSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Competitive Binding Assay: Competitive binding assay using ghrelin receptor.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 566.66, ALogP 3.63, HBA 7, HBD 4, PSA 134.16, QED 0.18
Compound (SMILES): COc1ccc(Cn2c([C@@H](Cc3ccccc3)NC(C)=O)nnc2[C@@H](Cc2c[nH]c3ccccc23)NC(=O)[C@@H]2CNCCO2)cc1
InChIKey: ZEWOKKRACQOIMW-IWWXRALLSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Competitive Binding Assay: Competitive binding assay using ghrelin receptor.
Measurement: IC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 621.74, ALogP 3.62, HBA 8, HBD 4, PSA 135.19, QED 0.17
Compound (SMILES): COc1ccc(Cn2c([C@@H](Cc3c[nH]c4ccccc34)NC(C)=O)nnc2[C@@H](Cc2c[nH]c3ccccc23)NC(=O)C(C)(C)N)cc1
InChIKey: OMEYXMRIYJZPAD-ROJLCIKYSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Competitive Binding Assay: Competitive binding assay using ghrelin receptor.
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 632.77, ALogP 4.85, HBA 7, HBD 5, PSA 155.74, QED 0.13
Compound (SMILES): COc1ccc(Cn2c([C@@H](Cc3c[nH]c4ccccc34)NC=O)nnc2[C@@H](Cc2c[nH]c3ccccc23)NC(=O)C(C)(C)N)cc1
InChIKey: DEQOTWGMVLLXTM-FIRIVFDPSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Competitive Binding Assay: Competitive binding assay using ghrelin receptor.
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 618.74, ALogP 4.46, HBA 7, HBD 5, PSA 155.74, QED 0.12
Compound (SMILES): CC(C)(CO)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCN5CCOCC5)ccc34)cc2)no1
InChIKey: BDDKOCILLICHON-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Binding Assay: Competition binding assay used herein were developed validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336.
Measurement: Kd = 0.69 nM (pChEMBL 9.15999984741211)
Descriptors: MW 576.68, ALogP 4.83, HBA 10, HBD 3, PSA 126.39, QED 0.23
Compound (SMILES): CC(CO)(CO)c1cc(NC(=O)Nc2ccc(-c3cn4c(n3)sc3cc(OCCN5CCOCC5)ccc34)cc2)no1
InChIKey: RWLXCDFZJDZLHX-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Binding Assay: Competition binding assay used herein were developed validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336.
Measurement: Kd = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 592.68, ALogP 3.8, HBA 11, HBD 4, PSA 146.62, QED 0.19
Compound (SMILES): CC(Cc1cccc(CCNC(=O)Cc2ccc(N(C)C(=O)CCN3CCC(OC(=O)Nc4ccccc4-c4ccccc4)CC3)cc2)c1)NC[C@H](O)c1ccc(O)c2[nH]c(=O)ccc12
InChIKey: JROFTQQUDINWSC-PTIAPEEWSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Radioligand Binding Assay: Radioligand binding assay using muscarinic receptors.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 879.07, ALogP 7.12, HBA 9, HBD 6, PSA 176.33, QED 0.05
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(CCNC[C@H](O)c3ccc(O)c4[nH]c(=O)ccc34)cc2)cc1N(C)C(=O)CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1
InChIKey: JORDOGYMROOYCP-SJARJILFSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Radioligand Binding Assay: Radioligand binding assay using muscarinic receptors.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 836.99, ALogP 7.39, HBA 9, HBD 6, PSA 176.33, QED 0.06
Compound (SMILES): CN(C)CCc1c[nH]c2ccc(/N=C(\N)c3cccs3)cc12
InChIKey: TZUMRJWGGAAQFU-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Enzyme Assay: Enzyme assay using recombinant human inducible NOS (iNOS), human endothelial constitutive NOS (eNOS) or human neuronal constitutive NOS (nNOS).
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 312.44, ALogP 3.37, HBA 3, HBD 2, PSA 57.41, QED 0.56
Compound (SMILES): CN(C)CCCc1c[nH]c2ccc(/N=C(\N)c3cccs3)cc12
InChIKey: SLZDCHGYGQWGAB-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Enzyme Assay: Enzyme assay using recombinant human inducible NOS (iNOS), human endothelial constitutive NOS (eNOS) or human neuronal constitutive NOS (nNOS).
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 326.47, ALogP 3.76, HBA 3, HBD 2, PSA 57.41, QED 0.54
Compound (SMILES): CCN1CCC(c2c[nH]c3ccc(/N=C(\N)c4cccs4)cc23)CC1
InChIKey: WDYQEZDEPNZBEW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine 1D receptor (SINGLE PROTEIN), Bos taurus
UniProt: Q8MI13
Assay: Binding Assay: 5-HT1D binding assays (agonist radioligand)were performed using bovine caudate membranes according to the methods of Heuring and Peroutka (J. Neurosci 1987, 7: 894-903). 5-HT1B (rat cerebral cortex) binding assays (agonist radioligand) were performed according to the method of Hoyer et. al. (Eur. J. Pharmacol. 1995, 118: 1-12).
Measurement: IC50 = 680 nM (pChEMBL 6.170000076293945)
Descriptors: MW 352.51, ALogP 4.47, HBA 3, HBD 2, PSA 57.41, QED 0.54
Compound (SMILES): CN1CCC[C@@H]1Cc1c[nH]c2ccc(/N=C(\N)c3cccs3)cc12
InChIKey: NXMUTZARWRLWNI-OAHLLOKOSA-N
Target: 5-hydroxytryptamine 1D receptor (SINGLE PROTEIN), Bos taurus
UniProt: Q8MI13
Assay: Binding Assay: 5-HT1D binding assays (agonist radioligand)were performed using bovine caudate membranes according to the methods of Heuring and Peroutka (J. Neurosci 1987, 7: 894-903). 5-HT1B (rat cerebral cortex) binding assays (agonist radioligand) were performed according to the method of Hoyer et. al. (Eur. J. Pharmacol. 1995, 118: 1-12).
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 338.48, ALogP 3.9, HBA 3, HBD 2, PSA 57.41, QED 0.56
Compound (SMILES): CN1CCC[C@H]1Cc1c[nH]c2ccc(/N=C(\N)c3cccs3)cc12
InChIKey: NXMUTZARWRLWNI-HNNXBMFYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Rattus norvegicus
UniProt: P28564
Assay: Binding Assay: 5-HT1D binding assays (agonist radioligand)were performed using bovine caudate membranes according to the methods of Heuring and Peroutka (J. Neurosci 1987, 7: 894-903). 5-HT1B (rat cerebral cortex) binding assays (agonist radioligand) were performed according to the method of Hoyer et. al. (Eur. J. Pharmacol. 1995, 118: 1-12).
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 338.48, ALogP 3.9, HBA 3, HBD 2, PSA 57.41, QED 0.56
Compound (SMILES): CN1CCC(c2c[nH]c3ccc(/N=C(\N)c4cccs4)cc23)C1
InChIKey: NWUGWNUIRGACCZ-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Enzyme Assay: Enzyme assay using recombinant human inducible NOS (iNOS), human endothelial constitutive NOS (eNOS) or human neuronal constitutive NOS (nNOS).
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 324.45, ALogP 3.69, HBA 3, HBD 2, PSA 57.41, QED 0.57
Compound (SMILES): CN1CCC(c2c[nH]c3ccc(/N=C(\N)c4ccco4)cc23)C1
InChIKey: HNZXYYYKZVJWFM-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Enzyme Assay: Enzyme assay using recombinant human inducible NOS (iNOS), human endothelial constitutive NOS (eNOS) or human neuronal constitutive NOS (nNOS).
Measurement: IC50 = 1240 nM (pChEMBL 5.909999847412109)
Descriptors: MW 308.38, ALogP 3.22, HBA 3, HBD 2, PSA 70.55, QED 0.58
Compound (SMILES): N[C@H]1C[C@@H](N2Cc3cnn(S(=O)(=O)C4CCCC4)c3C2)CO[C@@H]1c1cc(F)ccc1F
InChIKey: OQYMNVVXGACVAN-MFMILTCTSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Enzyme Assay: Enzyme assay using dipeptidyl peptidase-IV.
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 452.53, ALogP 2.45, HBA 7, HBD 1, PSA 90.45, QED 0.77
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(C)n2)cc1)N1CC[C@](CC(C)(C)O)(c2ccc(F)cc2)OC1=O
InChIKey: INMWFVJXYNMTDV-MYUZEXMDSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 479.55, ALogP 4.55, HBA 6, HBD 1, PSA 84.66, QED 0.56
Compound (SMILES): CCn1nc(-c2ccc([C@H](C)N3CC[C@](CC(C)(C)O)(c4ccccc4)OC3=O)cc2)ccc1=O
InChIKey: FLPLVVYBPARPKW-MMTVBGGISA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 475.59, ALogP 4.89, HBA 6, HBD 1, PSA 84.66, QED 0.53
Compound (SMILES): C[C@@H](c1ccc(-c2ccc(=O)n(CC(F)(F)F)n2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
InChIKey: CXOMREQXULTUTB-PPHZAIPVSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 529.56, ALogP 5.43, HBA 6, HBD 1, PSA 84.66, QED 0.44
Compound (SMILES): Cc1cc(-c2ccc([C@H](C)N3CC[C@](CC(C)(C)O)(c4ccccc4)OC3=O)cc2)nn(C)c1=O
InChIKey: CMRQSUMZGCSHON-MMTVBGGISA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Biological Assay Example 7: Using a procedure similar to that described in Biological Test Example 6, the inhibition of cytochrome P450 2C9-isoenzyme catalysed O-demethylation of [O-methyl-14C]-Naproxen by the test compound was assayed at 37° C. with human recombinant cytochrome P450 2C9.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 475.59, ALogP 4.72, HBA 6, HBD 1, PSA 84.66, QED 0.56