lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1c(OCCNc2ccccc2)nc(-c2ccncc2)cc1=O
InChIKey: SXFOPLYDZIVACR-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 99 nM (pChEMBL 7)
Descriptors: MW 322.37, ALogP 2.33, HBA 6, HBD 1, PSA 69.04, QED 0.71
Compound (SMILES): CCN(CCOc1nc(-c2ccncc2F)cc(=O)n1C)c1cccc(C)c1
InChIKey: JJVPFAOFVNZHDD-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 382.44, ALogP 3.2, HBA 6, HBD 0, PSA 60.25, QED 0.63
Compound (SMILES): CCN(CCOc1nc(-c2ccncn2)cc(=O)n1C)c1cccc(C)c1
InChIKey: DXSNGSGTMKJTPH-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 431.4 nM (pChEMBL 6.369999885559082)
Descriptors: MW 365.44, ALogP 2.45, HBA 7, HBD 0, PSA 73.14, QED 0.64
Compound (SMILES): Cn1c(OCCCc2cccnc2)nc(-c2ccncn2)cc1=O
InChIKey: FRGGZDFWFZNNJQ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 201 nM (pChEMBL 6.699999809265137)
Descriptors: MW 323.36, ALogP 1.64, HBA 7, HBD 0, PSA 82.79, QED 0.64
Compound (SMILES): Cn1c(O[C@H]2CC[C@H](c3ccc(CO)cc3)CC2)nc(-c2ccncn2)cc1=O
InChIKey: UUYZRMHDPAJSNF-IYARVYRRSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 115.3 nM (pChEMBL 6.940000057220459)
Descriptors: MW 392.46, ALogP 2.83, HBA 7, HBD 1, PSA 90.13, QED 0.72
Compound (SMILES): Cn1c(O[C@H]2CC[C@@H](c3ccc(CO)cc3)CC2)nc(-c2ccncn2)cc1=O
InChIKey: UUYZRMHDPAJSNF-HDICACEKSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 123.8 nM (pChEMBL 6.909999847412109)
Descriptors: MW 392.46, ALogP 2.83, HBA 7, HBD 1, PSA 90.13, QED 0.72
Compound (SMILES): CN1CCN(Cc2ccc([C@H]3CC[C@H](Oc4nc(-c5ccncn5)cc(=O)n4C)CC3)cc2)CC1
InChIKey: JGEVAUYSLPKMQL-YHBQERECSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 474.61, ALogP 3.09, HBA 8, HBD 0, PSA 76.38, QED 0.54
Compound (SMILES): CN1CCN(Cc2ccc([C@H]3CC[C@@H](Oc4nc(-c5ccncn5)cc(=O)n4C)CC3)cc2)CC1
InChIKey: JGEVAUYSLPKMQL-ZRZAMGCNSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 30.3 nM (pChEMBL 7.519999980926514)
Descriptors: MW 474.61, ALogP 3.09, HBA 8, HBD 0, PSA 76.38, QED 0.54
Compound (SMILES): CCCCCCc1ccc(Oc2nc(-c3ccncn3)cc(=O)n2C)cc1
InChIKey: OOGAFNVYTMIMPI-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 428.6 nM (pChEMBL 6.369999885559082)
Descriptors: MW 364.45, ALogP 4.15, HBA 6, HBD 0, PSA 69.9, QED 0.56
Compound (SMILES): CCCCCCOc1nc(-c2ccncc2)cc(=O)n1C
InChIKey: CUTVEPHNALKITM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 287.36, ALogP 2.8, HBA 5, HBD 0, PSA 57.01, QED 0.73
Compound (SMILES): Cn1c(O[C@H]2C[C@H]3CC[C@@H](C2)N3)nc(-c2ccncn2)cc1=O
InChIKey: ZLPJIFUXOYTFGH-GDNZZTSVSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 228.7 nM (pChEMBL 6.639999866485596)
Descriptors: MW 313.36, ALogP 0.9, HBA 7, HBD 1, PSA 81.93, QED 0.91
Compound (SMILES): Cn1c(O[C@H]2C[C@H]3CC[C@@H](C2)N3c2ccc(F)cc2)nc(-c2ccncn2)cc1=O
InChIKey: NKYHIBBKLWJKSQ-PIIMJCKOSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 236.5 nM (pChEMBL 6.630000114440918)
Descriptors: MW 407.45, ALogP 2.96, HBA 7, HBD 0, PSA 73.14, QED 0.66
Compound (SMILES): Cn1c(OC[C@H]2CCCN2C(=O)Oc2ccccc2)nc(-c2ccncn2)cc1=O
InChIKey: QQAQDBWNASHOAX-OAHLLOKOSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 56.4 nM (pChEMBL 7.25)
Descriptors: MW 407.43, ALogP 2.28, HBA 8, HBD 0, PSA 99.44, QED 0.64
Compound (SMILES): Cn1c(OC[C@H]2CCCN2c2ccc(F)cc2)nc(-c2ccncn2)cc1=O
InChIKey: AJWWKHQHTQWXKT-MRXNPFEDSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 157.9 nM (pChEMBL 6.800000190734863)
Descriptors: MW 381.41, ALogP 2.42, HBA 7, HBD 0, PSA 73.14, QED 0.68
Compound (SMILES): Cn1c(OC[C@H]2CCCN2c2ccc(F)cc2)nc(-c2ccncc2F)cc1=O
InChIKey: GQLOOXKUISSHOB-MRXNPFEDSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 43.1 nM (pChEMBL 7.369999885559082)
Descriptors: MW 398.41, ALogP 3.17, HBA 6, HBD 0, PSA 60.25, QED 0.66
Compound (SMILES): Cn1c(OC[C@@H]2CCCN2c2ccc(F)cc2)nc(-c2ccncn2)cc1=O
InChIKey: AJWWKHQHTQWXKT-INIZCTEOSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 37.6 nM (pChEMBL 7.420000076293945)
Descriptors: MW 381.41, ALogP 2.42, HBA 7, HBD 0, PSA 73.14, QED 0.68
Compound (SMILES): Cn1c(OC[C@@H]2CCCN2c2ccc(F)cc2)nc(-c2ccncc2F)cc1=O
InChIKey: GQLOOXKUISSHOB-INIZCTEOSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 18.4 nM (pChEMBL 7.739999771118164)
Descriptors: MW 398.41, ALogP 3.17, HBA 6, HBD 0, PSA 60.25, QED 0.66
Compound (SMILES): Cn1c(OC[C@H]2CCN(c3ccsc3)C2)nc(-c2ccncc2F)cc1=O
InChIKey: MXYNEGBCQKVKQT-ZDUSSCGKSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 73.2 nM (pChEMBL 7.130000114440918)
Descriptors: MW 386.45, ALogP 2.95, HBA 7, HBD 0, PSA 60.25, QED 0.67
Compound (SMILES): Cn1c(OC[C@H]2CCN(c3ccsc3)C2)nc(-c2ccncn2)cc1=O
InChIKey: SSJLOQGQVAAUSL-ZDUSSCGKSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 307.2 nM (pChEMBL 6.510000228881836)
Descriptors: MW 369.45, ALogP 2.2, HBA 8, HBD 0, PSA 73.14, QED 0.69
Compound (SMILES): Cn1c(OC[C@@H]2CCN(c3ccsc3)C2)nc(-c2ccncc2F)cc1=O
InChIKey: MXYNEGBCQKVKQT-CYBMUJFWSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 107.7 nM (pChEMBL 6.96999979019165)
Descriptors: MW 386.45, ALogP 2.95, HBA 7, HBD 0, PSA 60.25, QED 0.67
Compound (SMILES): Cn1c(OC[C@H]2CCN(c3ccccc3)C2)nc(-c2ccncn2)cc1=O
InChIKey: HIKQWMGBDQMZTD-HNNXBMFYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 941.3 nM (pChEMBL 6.03000020980835)
Descriptors: MW 363.42, ALogP 2.14, HBA 7, HBD 0, PSA 73.14, QED 0.69
Compound (SMILES): Cn1c(OC[C@H]2CCN(c3ccccc3)C2)nc(-c2ccncc2F)cc1=O
InChIKey: VDZQOEKMFAUPBW-HNNXBMFYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 134.1 nM (pChEMBL 6.869999885559082)
Descriptors: MW 380.42, ALogP 2.89, HBA 6, HBD 0, PSA 60.25, QED 0.68
Compound (SMILES): Cn1c(OC[C@@H]2CCN(c3ccccc3)C2)nc(-c2ccncc2F)cc1=O
InChIKey: VDZQOEKMFAUPBW-OAHLLOKOSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 658.5 nM (pChEMBL 6.179999828338623)
Descriptors: MW 380.42, ALogP 2.89, HBA 6, HBD 0, PSA 60.25, QED 0.68
Compound (SMILES): Cn1c(OCC(=O)c2ccccc2)nc(-c2ccncn2)cc1=O
InChIKey: QWAPOEXVTYKLGX-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 322.32, ALogP 1.5, HBA 7, HBD 0, PSA 86.97, QED 0.66
Compound (SMILES): Cn1c(OCCc2ccccc2)nc(-c2ccncn2)cc1=O
InChIKey: BRWFVIMKQBZRMY-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 308.34, ALogP 1.86, HBA 6, HBD 0, PSA 69.9, QED 0.72
Compound (SMILES): Cn1c(OCC(=O)c2ccc(Br)cc2)nc(-c2ccncc2F)cc1=O
InChIKey: BNGPSBMCEIFRPN-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 418.22, ALogP 3.01, HBA 6, HBD 0, PSA 74.08, QED 0.6
Compound (SMILES): Cn1c(OCC(=O)c2ccc(Br)cc2)nc(-c2ccncc2)cc1=O
InChIKey: ZSZSNFMZTDVRSQ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 400.23, ALogP 2.87, HBA 6, HBD 0, PSA 74.08, QED 0.62
Compound (SMILES): Cn1c(OCC(=O)c2ccc(Br)cc2)nc(-c2ccncn2)cc1=O
InChIKey: HLGJFFUUNXWONN-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 401.22, ALogP 2.26, HBA 7, HBD 0, PSA 86.97, QED 0.61
Compound (SMILES): Cn1c(OCCc2ccc(CN3CCCCC3)cc2)nc(-c2ccncc2)cc1=O
InChIKey: JRVLXWHZOKVMGQ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 404.51, ALogP 3.45, HBA 6, HBD 0, PSA 60.25, QED 0.6
Compound (SMILES): CN(C)Cc1ccc(CCOc2nc(-c3ccncc3)cc(=O)n2C)cc1
InChIKey: NDGDKGMWXSTRJP-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 364.45, ALogP 2.53, HBA 6, HBD 0, PSA 60.25, QED 0.64
Compound (SMILES): Cn1c(OCC2(c3ccccc3)OCCO2)nc(-c2ccncn2)cc1=O
InChIKey: XZASGEUHBUZUAY-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 386 nM (pChEMBL 6.409999847412109)
Descriptors: MW 366.38, ALogP 1.52, HBA 8, HBD 0, PSA 88.36, QED 0.68
Compound (SMILES): Cn1c(OCC(OC2CCCCO2)c2ccccc2)nc(-c2ccncn2)cc1=O
InChIKey: MZKZWPIZMPASPM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 349 nM (pChEMBL 6.460000038146973)
Descriptors: MW 408.46, ALogP 2.9, HBA 8, HBD 0, PSA 88.36, QED 0.59
Compound (SMILES): Cn1c(OC2CCN(c3cccc(CN4CCCCC4)c3)CC2)nc(-c2ccncn2)cc1=O
InChIKey: JQKYLDDGMMVILF-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta splice variant X1 (SINGLE PROTEIN), Bos taurus
UniProt: A0A059UE90
Assay: Inhibition Assay: A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM, .beta.-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 .mu.g/ml P-GS1, 41.7 .mu.M [.gamma.-.sup.32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25.degree. C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below.
Measurement: IC50 = 9.4 nM (pChEMBL 8.029999732971191)
Descriptors: MW 460.58, ALogP 3.27, HBA 8, HBD 0, PSA 76.38, QED 0.56
Compound (SMILES): CCN(c1cc(-c2ccc(OCCOC)cc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)C)CC1
InChIKey: YAYHRYAVXZWUIJ-OGESRWMOSA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition Assay: The potential inhibition of enzyme activities of human cytochromes P450 (CYP) of Compound 1, 2, or 105 was evaluated using pooled human liver microsomes.Methods: The competitive inhibition potential of Compounds 1, 2, and 105 was determined by assessing at multiple concentrations on probe CYP reactions near their respective Km values to create IC50 curves in human liver microsomes (HLM). The time-dependent inactivation (TDI) potential was also assessed for CYP3A4/5 by evaluating KI and kinact values when appropriate.A suspension containing PB, HLM, CYP-selective probe substrate, and the inhibitor being tested was added to a 96-well plate. The plates were preincubated in a 37Â° C. water bath for approximately 2 minutes. The reaction was initiated by the addition of NADPH to each well of the 96-well plate. The final concentrations for PB, HLM, and NADPH were 100 mmol/L (pH 7.4), 0.1 mg/mL, and 2.3 mmol/L, respectively. The CYP probe substrates and CYP inhibitors used as positive controls.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 588.79, ALogP 5.62, HBA 6, HBD 2, PSA 86.9, QED 0.27
Compound (SMILES): CCN(c1cc(C#CCN2CCOCC2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)[C@H]1CC[C@H](N(C)CCOC)CC1
InChIKey: XQFINGFCBFHOPE-WXUXXXNLSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition Assay: The potential inhibition of enzyme activities of human cytochromes P450 (CYP) of Compound 1, 2, or 105 was evaluated using pooled human liver microsomes.Methods: The competitive inhibition potential of Compounds 1, 2, and 105 was determined by assessing at multiple concentrations on probe CYP reactions near their respective Km values to create IC50 curves in human liver microsomes (HLM). The time-dependent inactivation (TDI) potential was also assessed for CYP3A4/5 by evaluating KI and kinact values when appropriate.A suspension containing PB, HLM, CYP-selective probe substrate, and the inhibitor being tested was added to a 96-well plate. The plates were preincubated in a 37Â° C. water bath for approximately 2 minutes. The reaction was initiated by the addition of NADPH to each well of the 96-well plate. The final concentrations for PB, HLM, and NADPH were 100 mmol/L (pH 7.4), 0.1 mg/mL, and 2.3 mmol/L, respectively. The CYP probe substrates and CYP inhibitors used as positive controls.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 605.82, ALogP 3.63, HBA 7, HBD 2, PSA 90.14, QED 0.38
Compound (SMILES): CCN(c1cc(C#CC2CCN(C)CC2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)C1CCOCC1
InChIKey: ZXYWTCVDQLRSRJ-UHFFFAOYSA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition Assay: The potential inhibition of enzyme activities of human cytochromes P450 (CYP) of Compound 1, 2, or 105 was evaluated using pooled human liver microsomes.Methods: The competitive inhibition potential of Compounds 1, 2, and 105 was determined by assessing at multiple concentrations on probe CYP reactions near their respective Km values to create IC50 curves in human liver microsomes (HLM). The time-dependent inactivation (TDI) potential was also assessed for CYP3A4/5 by evaluating KI and kinact values when appropriate.A suspension containing PB, HLM, CYP-selective probe substrate, and the inhibitor being tested was added to a 96-well plate. The plates were preincubated in a 37Â° C. water bath for approximately 2 minutes. The reaction was initiated by the addition of NADPH to each well of the 96-well plate. The final concentrations for PB, HLM, and NADPH were 100 mmol/L (pH 7.4), 0.1 mg/mL, and 2.3 mmol/L, respectively. The CYP probe substrates and CYP inhibitors used as positive controls.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 518.7, ALogP 3.93, HBA 5, HBD 2, PSA 77.67, QED 0.57
Compound (SMILES): CC(C)C1c2nc3ccc(S(C)(=O)=O)cc3n2CCN1c1nccc(C(F)(F)F)n1
InChIKey: SEQLXXRHDQNPMX-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Radioligand Binding Assay: Compounds of the invention were assessed in a competition binding assay where different concentrations of compounds were incubated with the LXR ligand binding domain (LBD) in the presence of radiolabeled LXR ligand [3H]TO901317. The amount of the LXR-LBD that complexed with [3H]T0901317 was measured by scintillation proximity assay (SPA) employing non-specific binding of LXR-LBD to poly-lysine coated Yttrium silicate beads. Partially purified LXR alpha or beta LBD protein (15-45 nM) was incubated at rt for 30 min with 15 nM [3H]TO901317 (25-40 Ci/mmol) and different concentrations of test compounds in 80 uL of phosphate buffered saline (PBS) buffer containing 2.5% DMSO, 1% glycerol, 2 mM EDTA, 2 mM CHAPS and 5 mM DTT in 96-well plates. Poly-lysine SPA beads (50 ug) were added to each well and the total volume was adjusted to 120 uL. The plates were shaken on an orbital shaker for 20 min and then allowed to settle for 10 more minutes at rt.
Measurement: Ki = 1770 nM (pChEMBL 5.75)
Descriptors: MW 439.46, ALogP 3.47, HBA 7, HBD 0, PSA 80.98, QED 0.62