lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCN(c1cc(-c2c(C)noc2C)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: PEBCQIHYGVTXHS-SOAUALDESA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 12.14 nM (pChEMBL 7.920000076293945)
Descriptors: MW 533.72, ALogP 5.2, HBA 6, HBD 2, PSA 94.47, QED 0.41
Compound (SMILES): CCN(c1cc(-c2cnn(C)c2C)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: BWHNKEYPTKLAIL-SOAUALDESA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 14.66 nM (pChEMBL 7.829999923706055)
Descriptors: MW 532.73, ALogP 4.64, HBA 6, HBD 2, PSA 86.26, QED 0.44
Compound (SMILES): CCN(c1cc(-c2ccn(C)n2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: RZGGFNAYUAXNPU-RQNOJGIXSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 4.71 nM (pChEMBL 8.329999923706055)
Descriptors: MW 518.71, ALogP 4.33, HBA 6, HBD 2, PSA 86.26, QED 0.46
Compound (SMILES): CCN(c1cc(-c2cccnc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: OXPZCLUKHFMKQN-DIVCQZSQSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 6.79 nM (pChEMBL 8.170000076293945)
Descriptors: MW 515.7, ALogP 4.99, HBA 5, HBD 2, PSA 81.33, QED 0.44
Compound (SMILES): CCN(c1cc(-c2ccc(-c3nn[nH]n3)cc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: AUJFBLHEAXEECH-MCZWQBSQSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 9.95 nM (pChEMBL 8)
Descriptors: MW 582.75, ALogP 4.78, HBA 7, HBD 3, PSA 122.9, QED 0.26
Compound (SMILES): CCN(c1cc(-c2cnc(C)nc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: MNRLYFJXPPCPDA-DIVCQZSQSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 5.14 nM (pChEMBL 8.289999961853027)
Descriptors: MW 530.72, ALogP 4.69, HBA 6, HBD 2, PSA 94.22, QED 0.44
Compound (SMILES): CCN(c1cc(-c2cn(C)nc2C)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: NJWZGGSDIVWDAI-SOAUALDESA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 4.98 nM (pChEMBL 8.300000190734863)
Descriptors: MW 532.73, ALogP 4.64, HBA 6, HBD 2, PSA 86.26, QED 0.44
Compound (SMILES): CCN(c1cc(-c2cscn2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: GHMHPEISUAMPLZ-YHBQERECSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 13.46 nM (pChEMBL 7.869999885559082)
Descriptors: MW 521.73, ALogP 5.05, HBA 6, HBD 2, PSA 81.33, QED 0.43
Compound (SMILES): CCN(c1cc(-c2cccs2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: MTXMCRMCPXGTAA-RQNOJGIXSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 7.96 nM (pChEMBL 8.100000381469727)
Descriptors: MW 520.74, ALogP 5.66, HBA 5, HBD 2, PSA 68.44, QED 0.4
Compound (SMILES): CCN(c1cc(-c2nccn2C)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: GVOQEUBNOYFOLH-RQNOJGIXSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 2.74 nM (pChEMBL 8.5600004196167)
Descriptors: MW 518.71, ALogP 4.33, HBA 6, HBD 2, PSA 86.26, QED 0.46
Compound (SMILES): CCN(c1cc(-c2ccc(N3CCN(C)CC3)nc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: VIAIEQMSVTZQEI-WXUXXXNLSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 1.63 nM (pChEMBL 8.789999961853027)
Descriptors: MW 613.85, ALogP 4.74, HBA 7, HBD 2, PSA 87.81, QED 0.36
Compound (SMILES): CCN(c1cc(-c2ccc(N3CCN(C)CC3)nc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)C1CCOCC1
InChIKey: VGTNAGNTWCIOCW-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 0.76 nM (pChEMBL 9.119999885559082)
Descriptors: MW 572.75, ALogP 4.05, HBA 7, HBD 2, PSA 93.8, QED 0.42
Compound (SMILES): CCN(c1cc(-c2ccc(N3CCNCC3)nc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: QBCNRVMPHQNKSE-OGESRWMOSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 4.21 nM (pChEMBL 8.380000114440918)
Descriptors: MW 599.82, ALogP 4.4, HBA 7, HBD 3, PSA 96.6, QED 0.34
Compound (SMILES): CCN(c1cc(-c2ccc(N3CCNCC3)nc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)C1CCOCC1
InChIKey: FTUGIYDOSRLWHX-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Test compounds were serially diluted 3-fold in DMSO in a 10 point-curve and 1 uL was spotted into a 384-well microplate in duplicate using a Platemate Plus equipped with 384-channel head (Thermo Scientific). The final top concentration of test compounds in the assay was 10 uM. Positive control (100% inhibition standard) was 1 mM final concentration of SAH and negative control (0% inhibition standard) contained 1 uL of DMSO. Test compounds were then incubated for 30 minutes with 40 uL per well of wild-type EZH2 (final concentration was 4 nM), Y641F EZH2 (final concentration was 0.1 nM) and A677G and A687V EZH2 (for each, final concentration was 2nM) and peptide in 1x assay buffer (20 mM BICINE pH =7.6, 1 mM DTT, 0.002% TWEEN 20 (generic: polysorbate 20), 0.005% BSG). For the wild-type EZH2 and A677G EZH2 assays, biotinylated peptide H3:21-44 with unmethylated K27 was present at a final concentration of 200 nM, while in the A687V EZH2 assay, biotinylated peptide H3.
Measurement: IC50 = 9.3 nM (pChEMBL 8.029999732971191)
Descriptors: MW 558.73, ALogP 3.71, HBA 7, HBD 3, PSA 102.59, QED 0.39
Compound (SMILES): CCN(c1cc(-c2cnccn2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: FIXJORJSCJZMFR-RQNOJGIXSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Test compounds were serially diluted 3-fold in DMSO in a 10 point-curve and 1 uL was spotted into a 384-well microplate in duplicate using a Platemate Plus equipped with 384-channel head (Thermo Scientific). The final top concentration of test compounds in the assay was 10 uM. Positive control (100% inhibition standard) was 1 mM final concentration of SAH and negative control (0% inhibition standard) contained 1 uL of DMSO. Test compounds were then incubated for 30 minutes with 40 uL per well of wild-type EZH2 (final concentration was 4 nM), Y641F EZH2 (final concentration was 0.1 nM) and A677G and A687V EZH2 (for each, final concentration was 2nM) and peptide in 1x assay buffer (20 mM BICINE pH =7.6, 1 mM DTT, 0.002% TWEEN 20 (generic: polysorbate 20), 0.005% BSG). For the wild-type EZH2 and A677G EZH2 assays, biotinylated peptide H3:21-44 with unmethylated K27 was present at a final concentration of 200 nM, while in the A687V EZH2 assay, biotinylated peptide H3.
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 516.69, ALogP 4.39, HBA 6, HBD 2, PSA 94.22, QED 0.46
Compound (SMILES): CCN(c1cc(-c2cnc(C)cn2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: DBJMXRJCUHUFBX-SOAUALDESA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Test compounds were serially diluted 3-fold in DMSO in a 10 point-curve and 1 uL was spotted into a 384-well microplate in duplicate using a Platemate Plus equipped with 384-channel head (Thermo Scientific). The final top concentration of test compounds in the assay was 10 uM. Positive control (100% inhibition standard) was 1 mM final concentration of SAH and negative control (0% inhibition standard) contained 1 uL of DMSO. Test compounds were then incubated for 30 minutes with 40 uL per well of wild-type EZH2 (final concentration was 4 nM), Y641F EZH2 (final concentration was 0.1 nM) and A677G and A687V EZH2 (for each, final concentration was 2nM) and peptide in 1x assay buffer (20 mM BICINE pH =7.6, 1 mM DTT, 0.002% TWEEN 20 (generic: polysorbate 20), 0.005% BSG). For the wild-type EZH2 and A677G EZH2 assays, biotinylated peptide H3:21-44 with unmethylated K27 was present at a final concentration of 200 nM, while in the A687V EZH2 assay, biotinylated peptide H3.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 530.72, ALogP 4.69, HBA 6, HBD 2, PSA 94.22, QED 0.44
Compound (SMILES): CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(-c2ccc(CN3CCOCC3)cc2)cc(N(CC)C2CCOCC2)c1C
InChIKey: GAYPXEWQCCLAHL-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Test compounds were serially diluted 3-fold in DMSO in a 10 point-curve and 1 uL was spotted into a 384-well microplate in duplicate using a Platemate Plus equipped with 384-channel head (Thermo Scientific). The final top concentration of test compounds in the assay was 10 uM. Positive control (100% inhibition standard) was 1 mM final concentration of SAH and negative control (0% inhibition standard) contained 1 uL of DMSO. Test compounds were then incubated for 30 minutes with 40 uL per well of wild-type EZH2 (final concentration was 4 nM), Y641F EZH2 (final concentration was 0.1 nM) and A677G and A687V EZH2 (for each, final concentration was 2nM) and peptide in 1x assay buffer (20 mM BICINE pH =7.6, 1 mM DTT, 0.002% TWEEN 20 (generic: polysorbate 20), 0.005% BSG). For the wild-type EZH2 and A677G EZH2 assays, biotinylated peptide H3:21-44 with unmethylated K27 was present at a final concentration of 200 nM, while in the A687V EZH2 assay, biotinylated peptide H3.
Measurement: IC50 = 10.4 nM (pChEMBL 7.980000019073486)
Descriptors: MW 600.8, ALogP 5.38, HBA 6, HBD 2, PSA 86.9, QED 0.31
Compound (SMILES): CCN(c1cc(-c2ccc(CN3CCOCC3)cc2)cc(C(=O)NCc2c(C)c(Br)c(C)[nH]c2=O)c1C)C1CCOCC1
InChIKey: OCCONAFXMOLOEB-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 3287.59 nM (pChEMBL 5.480000019073486)
Descriptors: MW 651.65, ALogP 5.5, HBA 6, HBD 2, PSA 86.9, QED 0.32
Compound (SMILES): CCN(c1cc(-c2ccc(CN3CCOCC3)cc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1Cl)C1CCOCC1
InChIKey: DGCNEYPMLOTXMG-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Test compounds were serially diluted 3-fold in DMSO in a 10 point-curve and 1 uL was spotted into a 384-well microplate in duplicate using a Platemate Plus equipped with 384-channel head (Thermo Scientific). The final top concentration of test compounds in the assay was 10 uM. Positive control (100% inhibition standard) was 1 mM final concentration of SAH and negative control (0% inhibition standard) contained 1 uL of DMSO. Test compounds were then incubated for 30 minutes with 40 uL per well of wild-type EZH2 (final concentration was 4 nM), Y641F EZH2 (final concentration was 0.1 nM) and A677G and A687V EZH2 (for each, final concentration was 2nM) and peptide in 1x assay buffer (20 mM BICINE pH =7.6, 1 mM DTT, 0.002% TWEEN 20 (generic: polysorbate 20), 0.005% BSG). For the wild-type EZH2 and A677G EZH2 assays, biotinylated peptide H3:21-44 with unmethylated K27 was present at a final concentration of 200 nM, while in the A687V EZH2 assay, biotinylated peptide H3.
Measurement: IC50 = 14.5 nM (pChEMBL 7.840000152587891)
Descriptors: MW 593.17, ALogP 5.08, HBA 6, HBD 2, PSA 86.9, QED 0.36
Compound (SMILES): CCN(c1cc(-c2ccc(CN3CCOCC3)cc2)cc(C(=O)NCc2c(C)c(F)c(C)[nH]c2=O)c1C)C1CCOCC1
InChIKey: MVMFNMZLRJXPHI-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Test compounds were serially diluted 3-fold in DMSO in a 10 point-curve and 1 uL was spotted into a 384-well microplate in duplicate using a Platemate Plus equipped with 384-channel head (Thermo Scientific). The final top concentration of test compounds in the assay was 10 uM. Positive control (100% inhibition standard) was 1 mM final concentration of SAH and negative control (0% inhibition standard) contained 1 uL of DMSO. Test compounds were then incubated for 30 minutes with 40 uL per well of wild-type EZH2 (final concentration was 4 nM), Y641F EZH2 (final concentration was 0.1 nM) and A677G and A687V EZH2 (for each, final concentration was 2nM) and peptide in 1x assay buffer (20 mM BICINE pH =7.6, 1 mM DTT, 0.002% TWEEN 20 (generic: polysorbate 20), 0.005% BSG). For the wild-type EZH2 and A677G EZH2 assays, biotinylated peptide H3:21-44 with unmethylated K27 was present at a final concentration of 200 nM, while in the A687V EZH2 assay, biotinylated peptide H3.
Measurement: IC50 = 183.5 nM (pChEMBL 6.739999771118164)
Descriptors: MW 590.74, ALogP 4.87, HBA 6, HBD 2, PSA 86.9, QED 0.37
Compound (SMILES): CCN(c1cc(-c2cn(C)cn2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: OIMQUIXLTMERHX-RQNOJGIXSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 8.07 nM (pChEMBL 8.09000015258789)
Descriptors: MW 518.71, ALogP 4.33, HBA 6, HBD 2, PSA 86.26, QED 0.46
Compound (SMILES): CCN(c1cc(-c2ccc(C(=O)N3CCC3)cc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: SBAQKAFXTIZCOI-WXUXXXNLSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 2.23 nM (pChEMBL 8.649999618530273)
Descriptors: MW 597.8, ALogP 5.44, HBA 5, HBD 2, PSA 88.75, QED 0.34
Compound (SMILES): CCN(c1cc(-c2ccc(C(=O)NCCCO)cc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: LPHBHYGFGVLDSX-WXUXXXNLSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 5.69 nM (pChEMBL 8.239999771118164)
Descriptors: MW 615.82, ALogP 4.71, HBA 6, HBD 4, PSA 117.77, QED 0.22
Compound (SMILES): CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(-c2ccc(N3CCN(C)CC3)nc2)cc(N(CC)C2CCOCC2)c1C
InChIKey: KAQCDEYIHYEDMG-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Test compounds were serially diluted 3-fold in DMSO in a 10 point-curve and 1 uL was spotted into a 384-well microplate in duplicate using a Platemate Plus equipped with 384-channel head (Thermo Scientific). The final top concentration of test compounds in the assay was 10 uM. Positive control (100% inhibition standard) was 1 mM final concentration of SAH and negative control (0% inhibition standard) contained 1 uL of DMSO. Test compounds were then incubated for 30 minutes with 40 uL per well of wild-type EZH2 (final concentration was 4 nM), Y641F EZH2 (final concentration was 0.1 nM) and A677G and A687V EZH2 (for each, final concentration was 2nM) and peptide in 1x assay buffer (20 mM BICINE pH =7.6, 1 mM DTT, 0.002% TWEEN 20 (generic: polysorbate 20), 0.005% BSG). For the wild-type EZH2 and A677G EZH2 assays, biotinylated peptide H3:21-44 with unmethylated K27 was present at a final concentration of 200 nM, while in the A687V EZH2 assay, biotinylated peptide H3.
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 600.81, ALogP 4.69, HBA 7, HBD 2, PSA 93.8, QED 0.35
Compound (SMILES): CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(-c2ccc(N3CCNCC3)nc2)cc(N(CC)C2CCOCC2)c1C
InChIKey: SMGSYCJYJLHFGP-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition Assay: Test compounds were serially diluted 3-fold in DMSO in a 10 point-curve and 1 uL was spotted into a 384-well microplate in duplicate using a Platemate Plus equipped with 384-channel head (Thermo Scientific). The final top concentration of test compounds in the assay was 10 uM. Positive control (100% inhibition standard) was 1 mM final concentration of SAH and negative control (0% inhibition standard) contained 1 uL of DMSO. Test compounds were then incubated for 30 minutes with 40 uL per well of wild-type EZH2 (final concentration was 4 nM), Y641F EZH2 (final concentration was 0.1 nM) and A677G and A687V EZH2 (for each, final concentration was 2nM) and peptide in 1x assay buffer (20 mM BICINE pH =7.6, 1 mM DTT, 0.002% TWEEN 20 (generic: polysorbate 20), 0.005% BSG). For the wild-type EZH2 and A677G EZH2 assays, biotinylated peptide H3:21-44 with unmethylated K27 was present at a final concentration of 200 nM, while in the A687V EZH2 assay, biotinylated peptide H3.
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 586.78, ALogP 4.35, HBA 7, HBD 3, PSA 102.59, QED 0.32
Compound (SMILES): CCN(c1cc(-c2ccc(N3CCNCC3)nc2)cc(C(=O)NCc2c(C(C)C)cc(C)[nH]c2=O)c1C)C1CCOCC1
InChIKey: NVAZSNXAXUCTPW-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 3.74 nM (pChEMBL 8.430000305175781)
Descriptors: MW 586.78, ALogP 4.52, HBA 7, HBD 3, PSA 102.59, QED 0.34
Compound (SMILES): CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(-c2ccc(N3CCN(C4CCN(C)CC4)CC3)nc2)cc(N(CC)C2CCOCC2)c1C
InChIKey: NWQWVNMSRQPVFF-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 1.82 nM (pChEMBL 8.739999771118164)
Descriptors: MW 683.94, ALogP 5.16, HBA 8, HBD 2, PSA 97.04, QED 0.29
Compound (SMILES): CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(-c2ccc(CN3CCOCC3)nc2)cc(N(CC)C2CCOCC2)c1C
InChIKey: VMJGSRBSELPABP-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 2.82 nM (pChEMBL 8.550000190734863)
Descriptors: MW 601.79, ALogP 4.77, HBA 7, HBD 2, PSA 99.79, QED 0.33
Compound (SMILES): CCN(c1cc(-c2ccc(N3CCC(N(C)C)CC3)nc2)cc(C(=O)NCc2c(C(C)C)cc(C)[nH]c2=O)c1C)C1CCOCC1
InChIKey: RMZUMPMWMNRRJH-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 628.86, ALogP 5.64, HBA 7, HBD 2, PSA 93.8, QED 0.3
Compound (SMILES): CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(-c2ccc(N3CCC(N(C)C)CC3)nc2)cc(N(CC)C2CCOCC2)c1C
InChIKey: BLNOPNCRRSAGEB-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were all performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 uL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2x3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 uL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 uL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control, A cocktail (40 uL) containing the wild-type PRC2 enzyme and H3K27me0 peptide or any of the Y641 mutant enzymes and H3K27me2 peptide was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25 C., then a cocktail (10 uL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 uL).
Measurement: IC50 = 5.36 nM (pChEMBL 8.270000457763672)
Descriptors: MW 628.86, ALogP 5.47, HBA 7, HBD 2, PSA 93.8, QED 0.29
Compound (SMILES): Cc1nccc(-c2ccc(C(=O)N3CCOCC3)c(Cl)c2)c1C#Cc1ccc(N)nc1
InChIKey: UDIUKSLSDVCBFN-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: HTS Assay: The GSK3beta primary screen was conducted in assay ready 1536 plates (Aurora 29847) that contain 2.5 mL/well of 10 mM compound. Human GSK3beta as a GST fusion expressed in baculoviral system was purchased from BPS Bioscience (San Diego, Calif.). The GSK3beta peptide substrate was from American Peptide (Sunnyvale, Calif.; Cat 311153). 1 L/well of CABPE (22.5 nM GSK3beta , 8 uM peptide in AB buffer (12.5 mM DTT, 0.25 mg/mL BSA, 0.5 unit/mL Heparin)), 0.5 L/well of 125 uM of ATP, and 1 L/well of positive control 50 uM of GW8510 (positive control) or AB (DMSO only neutral control) in respective wells according to plate design using BioRAPTR (Beckman, Brea, Calif.). Reactions were incubated at room temperature for 60 minutes. 2.5 uL/well of ADP-Glo (Promega, V9103) was added with BioRAPTR, and incubated at room temperature for 40 minutes followed by addition of 5 uL/well of ADP-Glo detection reagent (Promega, V9103) with Combi nL (Thermo, Waltham, Mass.).
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 432.91, ALogP 3.56, HBA 5, HBD 1, PSA 81.34, QED 0.63
Compound (SMILES): Cc1nccc(-c2ccc(C(=O)N(C)C)c(Cl)c2)c1C#Cc1ccc(N)nc1
InChIKey: MNHCYTKOZZNQIL-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: HTS Assay: The GSK3beta primary screen was conducted in assay ready 1536 plates (Aurora 29847) that contain 2.5 mL/well of 10 mM compound. Human GSK3beta as a GST fusion expressed in baculoviral system was purchased from BPS Bioscience (San Diego, Calif.). The GSK3beta peptide substrate was from American Peptide (Sunnyvale, Calif.; Cat 311153). 1 L/well of CABPE (22.5 nM GSK3beta , 8 uM peptide in AB buffer (12.5 mM DTT, 0.25 mg/mL BSA, 0.5 unit/mL Heparin)), 0.5 L/well of 125 uM of ATP, and 1 L/well of positive control 50 uM of GW8510 (positive control) or AB (DMSO only neutral control) in respective wells according to plate design using BioRAPTR (Beckman, Brea, Calif.). Reactions were incubated at room temperature for 60 minutes. 2.5 uL/well of ADP-Glo (Promega, V9103) was added with BioRAPTR, and incubated at room temperature for 40 minutes followed by addition of 5 uL/well of ADP-Glo detection reagent (Promega, V9103) with Combi nL (Thermo, Waltham, Mass.).
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 390.87, ALogP 3.79, HBA 4, HBD 1, PSA 72.11, QED 0.68
Compound (SMILES): Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(CF)COC2)o1
InChIKey: GDRHSCXKKDHHCK-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
Measurement: IC50 = 272 nM (pChEMBL 6.570000171661377)
Descriptors: MW 457.46, ALogP 2.47, HBA 8, HBD 3, PSA 121.11, QED 0.35
Compound (SMILES): CCC1(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)c2ccc(C)o2)COC1
InChIKey: DNAPDJCKXPGKFH-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
Measurement: IC50 = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 453.5, ALogP 2.91, HBA 8, HBD 3, PSA 121.11, QED 0.35
Compound (SMILES): Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N4CC[C@@H](O)C4)c3O)c(=O)c2=O)C2(C)COC2)o1
InChIKey: ZSBXLRVFHKRIHC-PDNQZYNLSA-N
Target: C-X-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25024
Assay: In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
Measurement: IC50 = 2620 nM (pChEMBL 5.579999923706055)
Descriptors: MW 481.51, ALogP 2.03, HBA 9, HBD 4, PSA 141.34, QED 0.29
Compound (SMILES): Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N4CC[C@H](O)C4)c3O)c(=O)c2=O)C2(C)COC2)o1
InChIKey: ZSBXLRVFHKRIHC-JRQMZCAUSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
Measurement: IC50 = 1088 nM (pChEMBL 5.960000038146973)
Descriptors: MW 481.51, ALogP 2.03, HBA 9, HBD 4, PSA 141.34, QED 0.29
Compound (SMILES): Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N4CCC[C@@H]4C(=O)OC(C)(C)C)c3O)c(=O)c2=O)C2(C)COC2)o1
InChIKey: SZNHUSHUOHAGBP-ICCFGIFFSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: In Vitro Assay: The in vitro affinity of the compounds of the present invention for the CXCR1 and CXCR2 receptors was determined on a functional test of the .beta.-arrestin recruitment type after receptor activation.It was demonstrated that the activation by CXCL8 of the CXCR2 receptor in cells of the PathHunter HEK293-CXCR2 line or of the CXCR1 receptor in cells of the U2OS h CXCR1 .beta.-arrestin line results in the recruitment of .beta.-arrestin (Richardson et al. 2003 Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J. Immunol. 170: 2904-2911.)In order to evaluate the direct interaction of the CXCR2 or CXCR1 receptor with .beta.-arrestin 2, a .beta.-arrestin 2 recruitment test for CXCR2 or CXCR1 based on of .beta.-galactosidase enzyme complementation (Olson K R, Eglen R M. Beta galactosidase complementation: a cell-based luminescent assay platform for drug discovery. Assay Drug Dev Technol. 2007 February; 5(1); 137-44).
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 565.62, ALogP 3.77, HBA 10, HBD 3, PSA 147.41, QED 0.21