lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(NC(=O)c2cc3c(C)nn(C4CCCCC4)c3s2)ccc1C(=O)N1CCC(O)CC1
InChIKey: FIMRVLDGXOGYFP-UHFFFAOYSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: Inhibition Assay: The PDE 7 (phosphodiesterase VII) inhibiting effect of the compounds of the present invention was performed by the following method, which was modified assay method described in Biochemical. Pharmacol. 48(6), 1219-1223 (1994).  (1) The active fraction of PDE 7 (phosphodiesterase VII) was obtained. That is, MOLT-4 (obtainable from ATCC as ATCC No. CRL-1582), which was cell line of human acute lymphoblastic lymphoma T cells, was incubated in RPMI1640 culture medium containing 10% fetal bovine serum to obtain 5x108 MOLT-4 cells. The cells were collected by centrifugation and suspended with 10 mL of buffer solution A [25 mM of tris-HCl, 5 mM of 2-mercaptoethnol, 2 mM of benzamidine, 2 mM of EDTA, 0.1 mM of 4-(2-aminoethyl)benzensulfonyl hydrochloride; pH 7.5], then homogenized by Polytron homogenizer. The homogenate were centrifuged under 25,000xG for 10 minutes at 4 C. The supernatant was separated and thus obtained supernatant was further centrifuged under 100,000xG for 60 minutes.
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 496.63, ALogP 4.77, HBA 7, HBD 2, PSA 96.69, QED 0.53
Compound (SMILES): COc1cc(NC(=O)c2cc3c(C)nn(C4CCCCC4)c3s2)ccc1C(=O)NCCO
InChIKey: HZLZDXOJTCLZKJ-UHFFFAOYSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: Inhibition Assay: The PDE 7 (phosphodiesterase VII) inhibiting effect of the compounds of the present invention was performed by the following method, which was modified assay method described in Biochemical. Pharmacol. 48(6), 1219-1223 (1994).  (1) The active fraction of PDE 7 (phosphodiesterase VII) was obtained. That is, MOLT-4 (obtainable from ATCC as ATCC No. CRL-1582), which was cell line of human acute lymphoblastic lymphoma T cells, was incubated in RPMI1640 culture medium containing 10% fetal bovine serum to obtain 5x108 MOLT-4 cells. The cells were collected by centrifugation and suspended with 10 mL of buffer solution A [25 mM of tris-HCl, 5 mM of 2-mercaptoethnol, 2 mM of benzamidine, 2 mM of EDTA, 0.1 mM of 4-(2-aminoethyl)benzensulfonyl hydrochloride; pH 7.5], then homogenized by Polytron homogenizer. The homogenate were centrifuged under 25,000xG for 10 minutes at 4 C. The supernatant was separated and thus obtained supernatant was further centrifuged under 100,000xG for 60 minutes.
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 456.57, ALogP 3.89, HBA 7, HBD 3, PSA 105.48, QED 0.5
Compound (SMILES): CNC(=O)c1ccc(NC(=O)c2cc3c(C)nn(C4CCCCC4)c3s2)cc1OC
InChIKey: SKTTUOBZRNOXLE-UHFFFAOYSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: Inhibition Assay: The PDE 7 (phosphodiesterase VII) inhibiting effect of the compounds of the present invention was performed by the following method, which was modified assay method described in Biochemical. Pharmacol. 48(6), 1219-1223 (1994).  (1) The active fraction of PDE 7 (phosphodiesterase VII) was obtained. That is, MOLT-4 (obtainable from ATCC as ATCC No. CRL-1582), which was cell line of human acute lymphoblastic lymphoma T cells, was incubated in RPMI1640 culture medium containing 10% fetal bovine serum to obtain 5x108 MOLT-4 cells. The cells were collected by centrifugation and suspended with 10 mL of buffer solution A [25 mM of tris-HCl, 5 mM of 2-mercaptoethnol, 2 mM of benzamidine, 2 mM of EDTA, 0.1 mM of 4-(2-aminoethyl)benzensulfonyl hydrochloride; pH 7.5], then homogenized by Polytron homogenizer. The homogenate were centrifuged under 25,000xG for 10 minutes at 4 C. The supernatant was separated and thus obtained supernatant was further centrifuged under 100,000xG for 60 minutes.
Measurement: IC50 = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 426.54, ALogP 4.53, HBA 6, HBD 2, PSA 85.25, QED 0.63
Compound (SMILES): CC1(c2cc(-c3sc(NC(=O)N4CCC[C@@]4(C)C(N)=O)nc3Cl)ccn2)CC1
InChIKey: DNULEWIOOBSRLM-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Kinase Assay: Typically frozen cells from 10 L of Tn5 cell culture were resuspended in Lysis Buffer 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 5 mM imidazole, 1 mM NaF, 0.1 ug/mL okadaic acid (OAA), 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free (20 tablets/1 L buffer, Roche Applied Sciences), benzonase (25 U/mL lysis buffer, EMD Biosciences) at a ratio of 1:10 v/v pellet to Lysis Buffer ratio, and mechanically lysed by douncing 20 strokes using a tight-fitting pestle. The lysate was centrifuged at 45,000 g for 30 minutes, and the supernatant was loaded onto a pre-equilibrated IMAC column (5 mL resin/100 mL lysate). The column was washed with 3-5 column volumes of Lysis Buffer, followed by a second wash of 3-5 column volumes with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 40 mM imidazole, 1 mM NaF, 0.1 ug/mL OAA, 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free. Protein was eluted with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 250 mM imidazole.
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 419.94, ALogP 3.78, HBA 5, HBD 2, PSA 101.21, QED 0.79
Compound (SMILES): CCCC1=NC=CC1c1cc(-c2cnc(NC(=O)N3CCCC3C(N)=O)s2)ccc1S(C)(=O)=O
InChIKey: YLXGHYNOVVAPOV-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Kinase Assay: Typically frozen cells from 10 L of Tn5 cell culture were resuspended in Lysis Buffer 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 5 mM imidazole, 1 mM NaF, 0.1 ug/mL okadaic acid (OAA), 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free (20 tablets/1 L buffer, Roche Applied Sciences), benzonase (25 U/mL lysis buffer, EMD Biosciences) at a ratio of 1:10 v/v pellet to Lysis Buffer ratio, and mechanically lysed by douncing 20 strokes using a tight-fitting pestle. The lysate was centrifuged at 45,000 g for 30 minutes, and the supernatant was loaded onto a pre-equilibrated IMAC column (5 mL resin/100 mL lysate). The column was washed with 3-5 column volumes of Lysis Buffer, followed by a second wash of 3-5 column volumes with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 40 mM imidazole, 1 mM NaF, 0.1 ug/mL OAA, 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free. Protein was eluted with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 250 mM imidazole.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 501.63, ALogP 3.55, HBA 7, HBD 2, PSA 134.82, QED 0.6
Compound (SMILES): CC(C)(C)c1nccc(-c2cnc(NC(=O)N3CCCC3C(N)=O)s2)n1
InChIKey: ILIMKGDDUBUFBN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Kinase Assay: Typically frozen cells from 10 L of Tn5 cell culture were resuspended in Lysis Buffer 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 5 mM imidazole, 1 mM NaF, 0.1 ug/mL okadaic acid (OAA), 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free (20 tablets/1 L buffer, Roche Applied Sciences), benzonase (25 U/mL lysis buffer, EMD Biosciences) at a ratio of 1:10 v/v pellet to Lysis Buffer ratio, and mechanically lysed by douncing 20 strokes using a tight-fitting pestle. The lysate was centrifuged at 45,000 g for 30 minutes, and the supernatant was loaded onto a pre-equilibrated IMAC column (5 mL resin/100 mL lysate). The column was washed with 3-5 column volumes of Lysis Buffer, followed by a second wash of 3-5 column volumes with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 40 mM imidazole, 1 mM NaF, 0.1 ug/mL OAA, 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free. Protein was eluted with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 250 mM imidazole.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 374.47, ALogP 2.38, HBA 6, HBD 2, PSA 114.1, QED 0.86
Compound (SMILES): CC(C)(C)c1cc(-c2cnc(NC(=O)N3CCCC3C(N)=O)s2)ccn1
InChIKey: OABGVOGTEPPXLG-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Kinase Assay: Typically frozen cells from 10 L of Tn5 cell culture were resuspended in Lysis Buffer 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 5 mM imidazole, 1 mM NaF, 0.1 ug/mL okadaic acid (OAA), 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free (20 tablets/1 L buffer, Roche Applied Sciences), benzonase (25 U/mL lysis buffer, EMD Biosciences) at a ratio of 1:10 v/v pellet to Lysis Buffer ratio, and mechanically lysed by douncing 20 strokes using a tight-fitting pestle. The lysate was centrifuged at 45,000 g for 30 minutes, and the supernatant was loaded onto a pre-equilibrated IMAC column (5 mL resin/100 mL lysate). The column was washed with 3-5 column volumes of Lysis Buffer, followed by a second wash of 3-5 column volumes with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 40 mM imidazole, 1 mM NaF, 0.1 ug/mL OAA, 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free. Protein was eluted with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 250 mM imidazole.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 373.48, ALogP 2.98, HBA 5, HBD 2, PSA 101.21, QED 0.86
Compound (SMILES): CC(C)(C)c1nccc(-c2cnc(NC(=O)N3CC4CC4C3C(N)=O)s2)n1
InChIKey: DMOPXNHLKVNOOY-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Kinase Assay: Typically frozen cells from 10 L of Tn5 cell culture were resuspended in Lysis Buffer 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 5 mM imidazole, 1 mM NaF, 0.1 ug/mL okadaic acid (OAA), 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free (20 tablets/1 L buffer, Roche Applied Sciences), benzonase (25 U/mL lysis buffer, EMD Biosciences) at a ratio of 1:10 v/v pellet to Lysis Buffer ratio, and mechanically lysed by douncing 20 strokes using a tight-fitting pestle. The lysate was centrifuged at 45,000 g for 30 minutes, and the supernatant was loaded onto a pre-equilibrated IMAC column (5 mL resin/100 mL lysate). The column was washed with 3-5 column volumes of Lysis Buffer, followed by a second wash of 3-5 column volumes with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 40 mM imidazole, 1 mM NaF, 0.1 ug/mL OAA, 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free. Protein was eluted with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 250 mM imidazole.
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 386.48, ALogP 2.24, HBA 6, HBD 2, PSA 114.1, QED 0.84
Compound (SMILES): CC1(c2cc(-c3cnc(NC(=O)N4CCC[C@]4(C)C(N)=O)s3)ccn2)CC1
InChIKey: SJNBGXFIKPBZKA-LJQANCHMSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Kinase Assay: Typically frozen cells from 10 L of Tn5 cell culture were resuspended in Lysis Buffer 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 5 mM imidazole, 1 mM NaF, 0.1 ug/mL okadaic acid (OAA), 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free (20 tablets/1 L buffer, Roche Applied Sciences), benzonase (25 U/mL lysis buffer, EMD Biosciences) at a ratio of 1:10 v/v pellet to Lysis Buffer ratio, and mechanically lysed by douncing 20 strokes using a tight-fitting pestle. The lysate was centrifuged at 45,000 g for 30 minutes, and the supernatant was loaded onto a pre-equilibrated IMAC column (5 mL resin/100 mL lysate). The column was washed with 3-5 column volumes of Lysis Buffer, followed by a second wash of 3-5 column volumes with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 40 mM imidazole, 1 mM NaF, 0.1 ug/mL OAA, 5 mM BME, 1 Complete protease inhibitor cocktail EDTA-free. Protein was eluted with 20 mM Tris-Cl, pH 7.5, 500 mM NaCl, 5% glycerol, 250 mM imidazole.
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 385.49, ALogP 3.13, HBA 5, HBD 2, PSA 101.21, QED 0.84
Compound (SMILES): C=CC(=O)N1CC2(CC(n3nc(-c4ccc(Oc5ccccc5)cc4)c4c(N)ncnc43)C2)C1
InChIKey: MDOOZFHNLMQRHG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 452.52, ALogP 4.22, HBA 7, HBD 1, PSA 99.16, QED 0.46
Compound (SMILES): CN(C)C/C=C/C(=O)N1CC2(CC(n3nc(-c4ccc(Oc5ccccc5)cc4)c4c(N)ncnc43)C2)C1
InChIKey: YSWLOVMGVYDHPU-RMKNXTFCSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 509.61, ALogP 4.15, HBA 8, HBD 1, PSA 102.4, QED 0.37
Compound (SMILES): CC#CC(=O)N1CC2(CC(n3nc(-c4ccc(Oc5ccccc5)cc4)c4c(N)ncnc43)C2)C1
InChIKey: OHWLBKVSYFITTM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 0.83 nM (pChEMBL 9.079999923706055)
Descriptors: MW 464.53, ALogP 4.05, HBA 7, HBD 1, PSA 99.16, QED 0.46
Compound (SMILES): Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)nn2C1CC2(C1)CN(C(=O)C1CO1)C2
InChIKey: GUNDXDNFPNCFDK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 468.52, ALogP 3.43, HBA 8, HBD 1, PSA 111.69, QED 0.45
Compound (SMILES): C=CC(=O)N1CCC2(CC(n3nc(-c4ccc(Oc5ccccc5)cc4)c4c(N)ncnc43)C2)C1
InChIKey: LGCTZXOAAXAAJU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 0.87 nM (pChEMBL 9.0600004196167)
Descriptors: MW 466.55, ALogP 4.61, HBA 7, HBD 1, PSA 99.16, QED 0.43
Compound (SMILES): C=CC(=O)N1CC2(CC(n3nc(-c4ccc(-c5cnc(Cc6ccccc6)n(C)c5=O)cc4F)c4c(N)ncnc43)C2)C1
InChIKey: VPAFMRVMSIUGST-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 0.85 nM (pChEMBL 9.069999694824219)
Descriptors: MW 576.64, ALogP 3.92, HBA 9, HBD 1, PSA 124.82, QED 0.3
Compound (SMILES): CC#CC(=O)N1CC2(CC(n3nc(-c4ccc(Oc5ccccc5)nc4)c4c(N)ncnc43)C2)C1
InChIKey: CCQOMYQXNWBYQO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 465.52, ALogP 3.45, HBA 8, HBD 1, PSA 112.05, QED 0.46
Compound (SMILES): C=CC(=O)N1CC2(CC(n3nc(-c4ccc(Oc5ccccc5)nc4)c4c(N)ncnc43)C2)C1
InChIKey: ULNOGMXQJHQDAB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 453.51, ALogP 3.61, HBA 8, HBD 1, PSA 112.05, QED 0.46
Compound (SMILES): C/C=C/C(=O)N1CC2(CC(n3nc(-c4ccc(Oc5ccccc5)nc4)c4c(N)ncnc43)C2)C1
InChIKey: OVALXEUVEWFZBY-QHHAFSJGSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 83 nM (pChEMBL 7.079999923706055)
Descriptors: MW 467.53, ALogP 4, HBA 8, HBD 1, PSA 112.05, QED 0.44
Compound (SMILES): C/C=C/C(=O)N1CC2(CC(n3nc(-c4ccc(Oc5ccccc5)cn4)c4c(N)ncnc43)C2)C1
InChIKey: PZKRNTLBXVZAJZ-QHHAFSJGSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 467.53, ALogP 4, HBA 8, HBD 1, PSA 112.05, QED 0.44
Compound (SMILES): C=CC(=O)N1CC2(CC(n3nc(-c4ccc(Oc5ccccc5)cn4)c4c(N)ncnc43)C2)C1
InChIKey: ZJFVKWGIIOZKBD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 453.51, ALogP 3.61, HBA 8, HBD 1, PSA 112.05, QED 0.46
Compound (SMILES): CC#CC(=O)N1CC2(CC(n3nc(-c4ccc(Oc5ccccc5)cn4)c4c(N)ncnc43)C2)C1
InChIKey: NMZYLIWWYXYUJR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 465.52, ALogP 3.45, HBA 8, HBD 1, PSA 112.05, QED 0.46
Compound (SMILES): CC#CC(=O)N1CC[C@]2(C1)C[C@@H](n1nc(-c3ccc(Oc4ccccc4)cn3)c3c(N)ncnc31)C2
InChIKey: YQPDSRXMSSPWMI-LIZUVYQKSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 0.74 nM (pChEMBL 9.130000114440918)
Descriptors: MW 479.54, ALogP 3.84, HBA 8, HBD 1, PSA 112.05, QED 0.44
Compound (SMILES): CC#CC(=O)N1CC[C@]2(C1)C[C@H](n1nc(-c3ccc(Oc4ccccc4)cn3)c3c(N)ncnc31)C2
InChIKey: YQPDSRXMSSPWMI-TULSRQJMSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 479.54, ALogP 3.84, HBA 8, HBD 1, PSA 112.05, QED 0.44
Compound (SMILES): CN(C)C/C=C/C(=O)N1CC2(CC(n3nc(-c4ccc(Oc5ccccc5)cn4)c4c(N)ncnc43)C2)C1
InChIKey: OMEHHTYNERJOKW-RMKNXTFCSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 510.6, ALogP 3.54, HBA 9, HBD 1, PSA 115.29, QED 0.38
Compound (SMILES): CN(C)C/C=C/C(=O)N1CC[C@]2(C1)C[C@@H](n1nc(-c3ccc(Oc4ccccc4)cn3)c3c(N)ncnc31)C2
InChIKey: SQMNUKCHENOODL-BXDGGBNXSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 524.63, ALogP 3.93, HBA 9, HBD 1, PSA 115.29, QED 0.36
Compound (SMILES): CN(C)C/C=C/C(=O)N1CC[C@]2(C1)C[C@H](n1nc(-c3ccc(Oc4ccccc4)cn3)c3c(N)ncnc31)C2
InChIKey: SQMNUKCHENOODL-JRAISMFPSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: HTRF Assay: An HTRF assay (Cisbio KinEASE-TK cat #62TKOPEC) was performed to quantitate the ability of test compounds to inhibit BTK mediated phosphorylation of substrate. Assays were assembled in 384 well plates where 6 nM of full-length human His-tagged BTK (Life Technologies cat #PV3587) and test compound at varying concentrations were preincubated for 15 minutes at 28Â° C. Then, 1 uM of TK substrate-biotin and 30 uM ATP were added and incubated for an additional 30 minutes at 28Â° C. Phospohrylation was detected by adding 62.5 nM Streptavidin-XL665 and TK-Antibody Cryptate diluted 1:100 in HTRF detection buffer (Cisbio cat #62SDBRDF) and incubated for 60 minutes at RT. The plate was read on an Envision plate reader and the fluoresence is measured at 620 nm (cryptate) and 665 nm (XL665). A ratio is calculated (665/620) and converted to POC relative to control and blank wells.Assay Buffer:50 mM HEPES (Invitrogen #15630), 0.01% Brij-35 (sigma #B4184), 10 mM MgC12 (Sigma M1028), 1 mM EGTA.
Measurement: IC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 524.63, ALogP 3.93, HBA 9, HBD 1, PSA 115.29, QED 0.36
Compound (SMILES): CC(Oc1cc(-c2cn(C3CCNCC3)nn2)cnc1N)c1c(Cl)ccc(F)c1Cl
InChIKey: NMJLXRYSZZFMOZ-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Enzyme Linked Immunosorbant Assay: (1) The enzyme reaction substrate Poly(Glu, Tyr) 4:1 was diluted to 20 ug/mL, 1254/well coated enzyme label plate with potassium ion-free PBS (10 mM sodium phosphate buffer, 150 mM NaCl, pH7.2-7.4), which was placed at 37 C. to allow to react for 12-16 h. The liquid in the wells was discarded. The plate was washed with 200 uL/well of T-PBS (potassium ion-free PBS containing 0.1% Tween-20) for three times (each for 5 min). The enzyme label plate was placed into a drying oven at 37 C. to dry for 1-2 h.(2) To each well was added 504 of ATP solution diluted with reaction buffer (50 mM HEPES pH 7.4, 50 mM MgCl2, 0.5 mM MnCl2, 0.2 mM Na3VO4, 1 mM DTT), and to each well was added 1 uL of the compounds. When adding the test compounds, 6 concentration gradients were set for each compound (the starting concentrations and dilution times were determined according to the results of preliminary screening so as to ensure that the maximum inhibition ratio was about 80%.
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 451.33, ALogP 4.43, HBA 7, HBD 2, PSA 90.88, QED 0.56
Compound (SMILES): C[C@H](Oc1cc(-c2cn(C3CCNCC3)nn2)cnc1N)c1c(Cl)ccc(F)c1Cl
InChIKey: NMJLXRYSZZFMOZ-NSHDSACASA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Enzyme Linked Immunosorbant Assay: (1) The enzyme reaction substrate Poly(Glu, Tyr) 4:1 was diluted to 20 ug/mL, 1254/well coated enzyme label plate with potassium ion-free PBS (10 mM sodium phosphate buffer, 150 mM NaCl, pH7.2-7.4), which was placed at 37 C. to allow to react for 12-16 h. The liquid in the wells was discarded. The plate was washed with 200 uL/well of T-PBS (potassium ion-free PBS containing 0.1% Tween-20) for three times (each for 5 min). The enzyme label plate was placed into a drying oven at 37 C. to dry for 1-2 h.(2) To each well was added 504 of ATP solution diluted with reaction buffer (50 mM HEPES pH 7.4, 50 mM MgCl2, 0.5 mM MnCl2, 0.2 mM Na3VO4, 1 mM DTT), and to each well was added 1 uL of the compounds. When adding the test compounds, 6 concentration gradients were set for each compound (the starting concentrations and dilution times were determined according to the results of preliminary screening so as to ensure that the maximum inhibition ratio was about 80%.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 451.33, ALogP 4.43, HBA 7, HBD 2, PSA 90.88, QED 0.56
Compound (SMILES): C[C@@H](Oc1cc(-c2cn(C3CCNCC3)nn2)cnc1N)c1c(Cl)ccc(F)c1Cl
InChIKey: NMJLXRYSZZFMOZ-LLVKDONJSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Enzyme Linked Immunosorbant Assay: (1) The enzyme reaction substrate Poly(Glu, Tyr) 4:1 was diluted to 20 ug/mL, 1254/well coated enzyme label plate with potassium ion-free PBS (10 mM sodium phosphate buffer, 150 mM NaCl, pH7.2-7.4), which was placed at 37 C. to allow to react for 12-16 h. The liquid in the wells was discarded. The plate was washed with 200 uL/well of T-PBS (potassium ion-free PBS containing 0.1% Tween-20) for three times (each for 5 min). The enzyme label plate was placed into a drying oven at 37 C. to dry for 1-2 h.(2) To each well was added 504 of ATP solution diluted with reaction buffer (50 mM HEPES pH 7.4, 50 mM MgCl2, 0.5 mM MnCl2, 0.2 mM Na3VO4, 1 mM DTT), and to each well was added 1 uL of the compounds. When adding the test compounds, 6 concentration gradients were set for each compound (the starting concentrations and dilution times were determined according to the results of preliminary screening so as to ensure that the maximum inhibition ratio was about 80%.
Measurement: IC50 = 11.7 nM (pChEMBL 7.929999828338623)
Descriptors: MW 451.33, ALogP 4.43, HBA 7, HBD 2, PSA 90.88, QED 0.56
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)C(C)C)cc4)c3)cnnc21
InChIKey: DZWMTGPUAKIKLC-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 31.1 nM (pChEMBL 7.510000228881836)
Descriptors: MW 424.5, ALogP 4.5, HBA 6, HBD 0, PSA 77.74, QED 0.47
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(C)(=O)=O)cc4F)c3)cnnc21
InChIKey: JBBFRNSUQWIIQO-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 10.9 nM (pChEMBL 7.960000038146973)
Descriptors: MW 414.44, ALogP 3.86, HBA 6, HBD 0, PSA 77.74, QED 0.51
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(N)(=O)=O)cc4)c3)cnnc21
InChIKey: HJWSOSQLQQNWPN-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 5.08 nM (pChEMBL 8.289999961853027)
Descriptors: MW 397.44, ALogP 2.97, HBA 6, HBD 1, PSA 103.76, QED 0.57
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)CC)cc4OC)c3)cnnc21
InChIKey: PTTQXDBPTFOCMT-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki < 2.47 nM (pChEMBL 8.607000350952148)
Descriptors: MW 440.5, ALogP 4.12, HBA 7, HBD 0, PSA 86.97, QED 0.45
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)C(C)C)cc4C#N)c3)cnnc21
InChIKey: ZXTANELFHSDZOB-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 449.51, ALogP 4.37, HBA 7, HBD 0, PSA 101.53, QED 0.45
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)C5CCC5)cc4OC)c3)cnnc21
InChIKey: QZVVTUGVJFSMAN-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 9.51 nM (pChEMBL 8.020000457763672)
Descriptors: MW 466.54, ALogP 4.65, HBA 7, HBD 0, PSA 86.97, QED 0.41
Compound (SMILES): CCn1cnc2c(-c3ccc(F)c(-c4ccc(S(=O)(=O)C5CC5)cc4OC)c3)cnnc21
InChIKey: LYBURRCIXUSBMB-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Radioligand Competition Binding Assay: The affinity of the test compounds was determined by radioligand competition binding assay, using the known compound [3H]Ro-15-1788 (Flumazenil) (Perkin Elmer, 85.4 Ci/mmol) and the human recombinant GABA A receptor containing the alpha2, beta2, and gamma3 subunits.Membranes were prepared from HEK cells expressing hGABA A alpha2beta2- gamma3 receptor, and validated to ascertain protein concentration, receptor expression and to determine the Kd of the flumazenil as well as the Ki of a standard set of compounds before being used to test new compounds.The assay was carried out in 96 well plates; testing compounds using a 10 point semi-log dilution range from 19 uM top concentration. 100 ul of radioligand and 100 ul of membrane in 50 mM Tris-HCI and 0.05% F127 with 1 ul of test compound was incubated for 2 hours to allow the reaction to achieve equilibrium, and then harvested onto filter plates, dried and counted on a TopCount NXT. The data was analysed, and the Ki values were presented.
Measurement: Ki = 9.71 nM (pChEMBL 8.010000228881836)
Descriptors: MW 452.51, ALogP 4.26, HBA 7, HBD 0, PSA 86.97, QED 0.43