lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H](Nc1ncnc2[nH]cnc12)c1nc2ccc(F)cn2c(=O)c1-c1ccccn1
InChIKey: GAGFVVAGSUEEKQ-LLVKDONJSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Alphascreen Assays : A PI3K Alphascreen assay (PerkinElmer, Waltham, Mass.) was used to measure the activity of a panel of four phosphoinositide 3-kinases: PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ. Enzyme reaction buffer was prepared using sterile water (Baxter, Deerfield, Ill.) and 50 mM Tris HCl pH 7, 14 mM MgCl2, 2 mM sodium cholate, and 100 mM NaCl. 2 mM DTT was added fresh the day of the experiment. The Alphascreen buffer was made using sterile water and 10 mM Tris HCl pH 7.5, 150 mM NaCl, 0.10% Tween 20, and 30 mM EDTA. 1 mM DTT was added fresh the day of the experiment. Compound source plates used for this assay were 384-well Greiner clear polypropylene plates containing test compounds at 5 mM and diluted 1:2 over 22 concentrations.
Measurement: Ki = 21452.2 nM (pChEMBL 4.670000076293945)
Descriptors: MW 402.39, ALogP 2.74, HBA 8, HBD 2, PSA 113.75, QED 0.48
Compound (SMILES): C[C@H](Nc1ncnc2[nH]cnc12)c1nc2ccc(F)cn2c(=O)c1-c1ccccn1
InChIKey: GAGFVVAGSUEEKQ-NSHDSACASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Alphascreen Assays : A PI3K Alphascreen assay (PerkinElmer, Waltham, Mass.) was used to measure the activity of a panel of four phosphoinositide 3-kinases: PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ. Enzyme reaction buffer was prepared using sterile water (Baxter, Deerfield, Ill.) and 50 mM Tris HCl pH 7, 14 mM MgCl2, 2 mM sodium cholate, and 100 mM NaCl. 2 mM DTT was added fresh the day of the experiment. The Alphascreen buffer was made using sterile water and 10 mM Tris HCl pH 7.5, 150 mM NaCl, 0.10% Tween 20, and 30 mM EDTA. 1 mM DTT was added fresh the day of the experiment. Compound source plates used for this assay were 384-well Greiner clear polypropylene plates containing test compounds at 5 mM and diluted 1:2 over 22 concentrations.
Measurement: Ki = 183.7 nM (pChEMBL 6.739999771118164)
Descriptors: MW 402.39, ALogP 2.74, HBA 8, HBD 2, PSA 113.75, QED 0.48
Compound (SMILES): CC(Nc1ncnc2[nH]cnc12)c1nc2ccc(F)cn2c(=O)c1-c1ccccn1
InChIKey: GAGFVVAGSUEEKQ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Alphascreen Assays : A PI3K Alphascreen assay (PerkinElmer, Waltham, Mass.) was used to measure the activity of a panel of four phosphoinositide 3-kinases: PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ. Enzyme reaction buffer was prepared using sterile water (Baxter, Deerfield, Ill.) and 50 mM Tris HCl pH 7, 14 mM MgCl2, 2 mM sodium cholate, and 100 mM NaCl. 2 mM DTT was added fresh the day of the experiment. The Alphascreen buffer was made using sterile water and 10 mM Tris HCl pH 7.5, 150 mM NaCl, 0.10% Tween 20, and 30 mM EDTA. 1 mM DTT was added fresh the day of the experiment. Compound source plates used for this assay were 384-well Greiner clear polypropylene plates containing test compounds at 5 mM and diluted 1:2 over 22 concentrations.
Measurement: Ki = 658.7 nM (pChEMBL 6.179999828338623)
Descriptors: MW 402.39, ALogP 2.74, HBA 8, HBD 2, PSA 113.75, QED 0.48
Compound (SMILES): C[C@@H](Nc1ncnc2[nH]cnc12)c1nc2ccc(F)cn2c(=O)c1-c1cccc(F)c1
InChIKey: RRTVCOAJMKLHDG-LLVKDONJSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Alphascreen Assays : A PI3K Alphascreen assay (PerkinElmer, Waltham, Mass.) was used to measure the activity of a panel of four phosphoinositide 3-kinases: PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ. Enzyme reaction buffer was prepared using sterile water (Baxter, Deerfield, Ill.) and 50 mM Tris HCl pH 7, 14 mM MgCl2, 2 mM sodium cholate, and 100 mM NaCl. 2 mM DTT was added fresh the day of the experiment. The Alphascreen buffer was made using sterile water and 10 mM Tris HCl pH 7.5, 150 mM NaCl, 0.10% Tween 20, and 30 mM EDTA. 1 mM DTT was added fresh the day of the experiment. Compound source plates used for this assay were 384-well Greiner clear polypropylene plates containing test compounds at 5 mM and diluted 1:2 over 22 concentrations.
Measurement: Ki = 19840 nM (pChEMBL 4.699999809265137)
Descriptors: MW 419.4, ALogP 3.48, HBA 7, HBD 2, PSA 100.86, QED 0.46
Compound (SMILES): C[C@H](Nc1ncnc2[nH]cnc12)c1nc2ccc(F)cn2c(=O)c1-c1cccc(F)c1
InChIKey: RRTVCOAJMKLHDG-NSHDSACASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Alphascreen Assays : A PI3K Alphascreen assay (PerkinElmer, Waltham, Mass.) was used to measure the activity of a panel of four phosphoinositide 3-kinases: PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ. Enzyme reaction buffer was prepared using sterile water (Baxter, Deerfield, Ill.) and 50 mM Tris HCl pH 7, 14 mM MgCl2, 2 mM sodium cholate, and 100 mM NaCl. 2 mM DTT was added fresh the day of the experiment. The Alphascreen buffer was made using sterile water and 10 mM Tris HCl pH 7.5, 150 mM NaCl, 0.10% Tween 20, and 30 mM EDTA. 1 mM DTT was added fresh the day of the experiment. Compound source plates used for this assay were 384-well Greiner clear polypropylene plates containing test compounds at 5 mM and diluted 1:2 over 22 concentrations.
Measurement: Ki = 110.1 nM (pChEMBL 6.960000038146973)
Descriptors: MW 419.4, ALogP 3.48, HBA 7, HBD 2, PSA 100.86, QED 0.46
Compound (SMILES): CC(Nc1ncnc2[nH]cnc12)c1nc2ccc(F)cn2c(=O)c1-c1cccc(F)c1
InChIKey: RRTVCOAJMKLHDG-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Alphascreen Assays : A PI3K Alphascreen assay (PerkinElmer, Waltham, Mass.) was used to measure the activity of a panel of four phosphoinositide 3-kinases: PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ. Enzyme reaction buffer was prepared using sterile water (Baxter, Deerfield, Ill.) and 50 mM Tris HCl pH 7, 14 mM MgCl2, 2 mM sodium cholate, and 100 mM NaCl. 2 mM DTT was added fresh the day of the experiment. The Alphascreen buffer was made using sterile water and 10 mM Tris HCl pH 7.5, 150 mM NaCl, 0.10% Tween 20, and 30 mM EDTA. 1 mM DTT was added fresh the day of the experiment. Compound source plates used for this assay were 384-well Greiner clear polypropylene plates containing test compounds at 5 mM and diluted 1:2 over 22 concentrations.
Measurement: Ki = 360.3 nM (pChEMBL 6.440000057220459)
Descriptors: MW 419.4, ALogP 3.48, HBA 7, HBD 2, PSA 100.86, QED 0.46
Compound (SMILES): CCOC[C@]1(c2nnc(C)o2)N[C@@H](c2nc(-c3ccc(F)cn3)c[nH]2)Cc2c1[nH]c1ccccc21
InChIKey: CHMXVWCAPWMNFD-NLFFAJNJSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Binding Scintillation Proximity Assay: The receptor-ligand binding Scintillation Proximity Assay (SPA) (N. D. Cook. Drug Discovery Today 1 (1996), pp. 287-294) for SSTR3 was performed with membranes isolated from Chinese hamster ovary (CHO)-K1 cells stably expressing the cloned human somatostatin receptors. Binding assays were performed in 384 well format using 125I-SS14 as the radioligand for SSTR3. The assay buffer consisted of 50 mM TrisHCl (pH 7.8) with 1 mM EGTA, 5 mM MgCl2, leupeptin (10 μg/mL), pepstatin (10 μg/mL), bacitracin (200 μg/mL), and aprotinin (0.5 μg/mL). CHO-K1 cell membranes were prebound to SPA beads and incubated with unlabelled test compounds and radiolabeled somatostatin in assay buffer. After 5 hours at room temperature, cpm/well was determined. Test compounds were examined in 10 point titrations over a range of concentrations from 0.00001 nM to 1200 nM. Percent inhibition was determined for each data point using binding in the presence of DMSO as the maximum achievable value.
Measurement: IC50 = 43.8 nM (pChEMBL 7.360000133514404)
Descriptors: MW 473.51, ALogP 3.95, HBA 7, HBD 3, PSA 117.54, QED 0.34
Compound (SMILES): CCOC[C@@]1(c2nnc(C)o2)N[C@@H](c2nc(-c3ccc(F)cn3)c[nH]2)Cc2c1[nH]c1ccccc21
InChIKey: CHMXVWCAPWMNFD-CJFMBICVSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Binding Scintillation Proximity Assay: The receptor-ligand binding Scintillation Proximity Assay (SPA) (N. D. Cook. Drug Discovery Today 1 (1996), pp. 287-294) for SSTR3 was performed with membranes isolated from Chinese hamster ovary (CHO)-K1 cells stably expressing the cloned human somatostatin receptors. Binding assays were performed in 384 well format using 125I-SS14 as the radioligand for SSTR3. The assay buffer consisted of 50 mM TrisHCl (pH 7.8) with 1 mM EGTA, 5 mM MgCl2, leupeptin (10 μg/mL), pepstatin (10 μg/mL), bacitracin (200 μg/mL), and aprotinin (0.5 μg/mL). CHO-K1 cell membranes were prebound to SPA beads and incubated with unlabelled test compounds and radiolabeled somatostatin in assay buffer. After 5 hours at room temperature, cpm/well was determined. Test compounds were examined in 10 point titrations over a range of concentrations from 0.00001 nM to 1200 nM. Percent inhibition was determined for each data point using binding in the presence of DMSO as the maximum achievable value.
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 473.51, ALogP 3.95, HBA 7, HBD 3, PSA 117.54, QED 0.34
Compound (SMILES): Cc1nnc(C2(C3CCCO3)N[C@@H](c3nc(-c4ccc(F)c(C)n4)c[nH]3)Cc3c2[nH]c2ccccc32)o1
InChIKey: WOVWSFKNIFKOFZ-ACRQWNCLSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Binding Scintillation Proximity Assay: The receptor-ligand binding Scintillation Proximity Assay (SPA) (N. D. Cook. Drug Discovery Today 1 (1996), pp. 287-294) for SSTR3 was performed with membranes isolated from Chinese hamster ovary (CHO)-K1 cells stably expressing the cloned human somatostatin receptors. Binding assays were performed in 384 well format using 125I-SS14 as the radioligand for SSTR3. The assay buffer consisted of 50 mM TrisHCl (pH 7.8) with 1 mM EGTA, 5 mM MgCl2, leupeptin (10 μg/mL), pepstatin (10 μg/mL), bacitracin (200 μg/mL), and aprotinin (0.5 μg/mL). CHO-K1 cell membranes were prebound to SPA beads and incubated with unlabelled test compounds and radiolabeled somatostatin in assay buffer. After 5 hours at room temperature, cpm/well was determined. Test compounds were examined in 10 point titrations over a range of concentrations from 0.00001 nM to 1200 nM. Percent inhibition was determined for each data point using binding in the presence of DMSO as the maximum achievable value.
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 499.55, ALogP 4.4, HBA 7, HBD 3, PSA 117.54, QED 0.34
Compound (SMILES): Cc1nnc(C2(C3CCCCO3)N[C@@H](c3nc(-c4ccc(F)c(C)n4)c[nH]3)Cc3c2[nH]c2ccccc32)o1
InChIKey: JHBLCTYNEYZOPF-LBOQJQFVSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Binding Scintillation Proximity Assay: The receptor-ligand binding Scintillation Proximity Assay (SPA) (N. D. Cook. Drug Discovery Today 1 (1996), pp. 287-294) for SSTR3 was performed with membranes isolated from Chinese hamster ovary (CHO)-K1 cells stably expressing the cloned human somatostatin receptors. Binding assays were performed in 384 well format using 125I-SS14 as the radioligand for SSTR3. The assay buffer consisted of 50 mM TrisHCl (pH 7.8) with 1 mM EGTA, 5 mM MgCl2, leupeptin (10 μg/mL), pepstatin (10 μg/mL), bacitracin (200 μg/mL), and aprotinin (0.5 μg/mL). CHO-K1 cell membranes were prebound to SPA beads and incubated with unlabelled test compounds and radiolabeled somatostatin in assay buffer. After 5 hours at room temperature, cpm/well was determined. Test compounds were examined in 10 point titrations over a range of concentrations from 0.00001 nM to 1200 nM. Percent inhibition was determined for each data point using binding in the presence of DMSO as the maximum achievable value.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 513.58, ALogP 4.79, HBA 7, HBD 3, PSA 117.54, QED 0.32
Compound (SMILES): COC1CC2C(C1)C2C1(c2nnc(C)o2)N[C@@H](c2nc(-c3ccc(F)c(C)n3)c[nH]2)Cc2c1[nH]c1ccccc21
InChIKey: XNXQXEOUZQFKHF-QAXVPUKQSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Binding Scintillation Proximity Assay: The receptor-ligand binding Scintillation Proximity Assay (SPA) (N. D. Cook. Drug Discovery Today 1 (1996), pp. 287-294) for SSTR3 was performed with membranes isolated from Chinese hamster ovary (CHO)-K1 cells stably expressing the cloned human somatostatin receptors. Binding assays were performed in 384 well format using 125I-SS14 as the radioligand for SSTR3. The assay buffer consisted of 50 mM TrisHCl (pH 7.8) with 1 mM EGTA, 5 mM MgCl2, leupeptin (10 μg/mL), pepstatin (10 μg/mL), bacitracin (200 μg/mL), and aprotinin (0.5 μg/mL). CHO-K1 cell membranes were prebound to SPA beads and incubated with unlabelled test compounds and radiolabeled somatostatin in assay buffer. After 5 hours at room temperature, cpm/well was determined. Test compounds were examined in 10 point titrations over a range of concentrations from 0.00001 nM to 1200 nM. Percent inhibition was determined for each data point using binding in the presence of DMSO as the maximum achievable value.
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 539.62, ALogP 4.89, HBA 7, HBD 3, PSA 117.54, QED 0.29
Compound (SMILES): COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)O)C[C@H]5/C=C\CCCCOC(=O)N4C3)cc(-c3ccccc3)nc2c1
InChIKey: ZNKKFPUPLGASNG-BHHHAAIVSA-N
Target: Hepatitis C virus serine protease, NS3/NS4A (PROTEIN COMPLEX), Hepatitis C virus
UniProt: D2K2A8
Assay: Enzymatic assay: The aim of this in vitro assay was to measure the inhibition of HCV NS3/4A protease complexes by the compounds of the present invention. This assay provides an indication of how effective compounds of the present invention would be in inhibiting HCV NS3/4A proteolytic activity. The inhibition of full-length hepatitis C NS3 protease enzyme was measured essentially as described in Poliakov, 2002 Prot Expression & Purification 25 363 371. Briefly, the hydrolysis of a depsipeptide substrate, Ac-DED(Edans)EEAbu-y-[COO]ASK(Dabcyl)-NH2 (AnaSpec, San Jose, USA), was measured spectrofluorometrically in the presence of a peptide cofactor, KKGSVVIVGRIVLSGK (Ake Engstrom, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden). [Landro, 1997 #Biochem 36 9340-9348]. The enzyme (1 nM) was incubated in 50 mM HEPES, pH 7.5, 10 mM DTT, 40% glycerol, 0.1% n-octyl-D-glucoside, with 25 uM NS4A cofactor and inhibitor at 30 C. for 10 min.
Measurement: Ki = 1070 nM (pChEMBL 5.96999979019165)
Descriptors: MW 571.63, ALogP 4.57, HBA 7, HBD 2, PSA 127.29, QED 0.43
Compound (SMILES): COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)O)C[C@H]5/C=C\CCCCOC(=O)N4C3)nc(Cl)cc2c1
InChIKey: XQNSGMJILVCEJU-RKSFHJAHSA-N
Target: Hepatitis C virus serine protease, NS3/NS4A (PROTEIN COMPLEX), Hepatitis C virus
UniProt: D2K2A8
Assay: Enzymatic assay: The aim of this in vitro assay was to measure the inhibition of HCV NS3/4A protease complexes by the compounds of the present invention. This assay provides an indication of how effective compounds of the present invention would be in inhibiting HCV NS3/4A proteolytic activity. The inhibition of full-length hepatitis C NS3 protease enzyme was measured essentially as described in Poliakov, 2002 Prot Expression & Purification 25 363 371. Briefly, the hydrolysis of a depsipeptide substrate, Ac-DED(Edans)EEAbu-y-[COO]ASK(Dabcyl)-NH2 (AnaSpec, San Jose, USA), was measured spectrofluorometrically in the presence of a peptide cofactor, KKGSVVIVGRIVLSGK (Ake Engstrom, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden). [Landro, 1997 #Biochem 36 9340-9348]. The enzyme (1 nM) was incubated in 50 mM HEPES, pH 7.5, 10 mM DTT, 40% glycerol, 0.1% n-octyl-D-glucoside, with 25 uM NS4A cofactor and inhibitor at 30 C. for 10 min.
Measurement: Ki = 1000 nM (pChEMBL 6)
Descriptors: MW 529.98, ALogP 3.55, HBA 7, HBD 2, PSA 127.29, QED 0.45
Compound (SMILES): COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)NS(=O)(=O)C6CC6)C[C@H]5/C=C\CCCCOC(=O)N4C3)nc(Cl)cc2c1
InChIKey: KMRSRQTYTCFVAX-LTYXBVNVSA-N
Target: Hepatitis C virus serine protease, NS3/NS4A (PROTEIN COMPLEX), Hepatitis C virus
UniProt: D2K2A8
Assay: Enzymatic assay: The aim of this in vitro assay was to measure the inhibition of HCV NS3/4A protease complexes by the compounds of the present invention. This assay provides an indication of how effective compounds of the present invention would be in inhibiting HCV NS3/4A proteolytic activity. The inhibition of full-length hepatitis C NS3 protease enzyme was measured essentially as described in Poliakov, 2002 Prot Expression & Purification 25 363 371. Briefly, the hydrolysis of a depsipeptide substrate, Ac-DED(Edans)EEAbu-y-[COO]ASK(Dabcyl)-NH2 (AnaSpec, San Jose, USA), was measured spectrofluorometrically in the presence of a peptide cofactor, KKGSVVIVGRIVLSGK (Ake Engstrom, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden). [Landro, 1997 #Biochem 36 9340-9348]. The enzyme (1 nM) was incubated in 50 mM HEPES, pH 7.5, 10 mM DTT, 40% glycerol, 0.1% n-octyl-D-glucoside, with 25 uM NS4A cofactor and inhibitor at 30 C. for 10 min.
Measurement: Ki = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 633.12, ALogP 3.08, HBA 9, HBD 2, PSA 153.23, QED 0.36
Compound (SMILES): COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)O)C[C@H]5/C=C\CCCCCOC(=O)N4C3)cc(-c3ccccc3)nc2c1
InChIKey: AWQPGSZGZVXQPF-WKELZURCSA-N
Target: Hepatitis C virus serine protease, NS3/NS4A (PROTEIN COMPLEX), Hepatitis C virus
UniProt: D2K2A8
Assay: Enzymatic assay: The aim of this in vitro assay was to measure the inhibition of HCV NS3/4A protease complexes by the compounds of the present invention. This assay provides an indication of how effective compounds of the present invention would be in inhibiting HCV NS3/4A proteolytic activity. The inhibition of full-length hepatitis C NS3 protease enzyme was measured essentially as described in Poliakov, 2002 Prot Expression & Purification 25 363 371. Briefly, the hydrolysis of a depsipeptide substrate, Ac-DED(Edans)EEAbu-y-[COO]ASK(Dabcyl)-NH2 (AnaSpec, San Jose, USA), was measured spectrofluorometrically in the presence of a peptide cofactor, KKGSVVIVGRIVLSGK (Ake Engstrom, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden). [Landro, 1997 #Biochem 36 9340-9348]. The enzyme (1 nM) was incubated in 50 mM HEPES, pH 7.5, 10 mM DTT, 40% glycerol, 0.1% n-octyl-D-glucoside, with 25 uM NS4A cofactor and inhibitor at 30 C. for 10 min.
Measurement: Ki = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 585.66, ALogP 4.96, HBA 7, HBD 2, PSA 127.29, QED 0.4
Compound (SMILES): COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)O)C[C@H]5/C=C\CCCCN(C)C(=O)[C@@H]4C3)cc(-c3nc(C(C)C)cs3)nc2c1Cl
InChIKey: DGROTVCEUFXOSG-DTMGCTNBSA-N
Target: Hepatitis C virus serine protease, NS3/NS4A (PROTEIN COMPLEX), Hepatitis C virus
UniProt: D2K2A8
Assay: Enzymatic Assay: The aim of this in vitro assay was to measure the inhibition of HCV NS3/4A protease complexes by the compounds of the present invention. This assay provides an indication of how effective compounds of the present invention would be in inhibiting HCV NS3/4A proteolytic activity. The inhibition of full-length hepatitis C NS3 protease enzyme was measured essentially as described in Poliakov, 2002 Prot Expression & Purification 25 363 371. Briefly, the hydrolysis of a depsipeptide substrate,Â  Ac-DED(Edans)EEAbuÃ[COO]ASK(Dabcyl)-NH2 (AnaSpec, San Jose, USA), was measured spectrofluorometrically in the presence of a peptide cofactor, KKGSVVIVGRIVLSGK (Ã¢ Â«ke Engstrom, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden). [Landro, 1997 #Biochem 36 9340-9348].
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 667.23, ALogP 6.08, HBA 8, HBD 2, PSA 130.95, QED 0.3
Compound (SMILES): O=C(O)CCc1nnc(Cc2nc3ccc(-c4ccccc4)cc3s2)o1
InChIKey: ZMFSFVPWWUDQFF-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 365.41, ALogP 3.95, HBA 6, HBD 1, PSA 89.11, QED 0.56
Compound (SMILES): CS(=O)(=O)NCc1nnc(Cc2nc3ccc(-c4ccccc4)cc3s2)o1
InChIKey: FOJPTABWHWIDRG-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 400.49, ALogP 2.99, HBA 7, HBD 1, PSA 97.98, QED 0.53
Compound (SMILES): N#CCCc1nnc(Cc2nc3ccc(-c4ccccc4)cc3s2)o1
InChIKey: GPFCMEAOSKEXNI-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 346.42, ALogP 4.39, HBA 6, HBD 0, PSA 75.6, QED 0.54
Compound (SMILES): O=C(Cc1nnc(Cc2nc3ccc(-c4ccccc4)cc3s2)o1)NCCO
InChIKey: UQQVVWIAWCOYJS-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 83 nM (pChEMBL 7.079999923706055)
Descriptors: MW 394.46, ALogP 2.59, HBA 7, HBD 2, PSA 101.14, QED 0.5
Compound (SMILES): N#CCNC(=O)Cc1nnc(Cc2nc3cc(-c4ccccc4)ccc3o2)o1
InChIKey: FJQIRAGASNBDOM-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 373.37, ALogP 2.65, HBA 7, HBD 1, PSA 117.84, QED 0.52
Compound (SMILES): O=C(Cc1nnc(Cc2nc3ccc(-c4ccccc4)cc3s2)o1)N1CCOCC1
InChIKey: LNELRILHDXQTGG-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 420.49, ALogP 3.34, HBA 7, HBD 0, PSA 81.35, QED 0.49
Compound (SMILES): O=C(Cc1nnc(Cc2nc3ccc(-c4ccccc4)cc3s2)o1)Nc1ccccc1
InChIKey: YXYQLNOCZAJRBA-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 426.5, ALogP 5.12, HBA 6, HBD 1, PSA 80.91, QED 0.41
Compound (SMILES): NS(=O)(=O)NCc1nnc(Cc2nc3ccc(-c4ccccc4)cc3s2)o1
InChIKey: YGZCJOQFMJZVDF-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition of endothelial lipase in human HT1080 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins in presence of C57BL/6 mouse plasma by fluorescence assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 401.47, ALogP 2.23, HBA 7, HBD 2, PSA 124, QED 0.51
Compound (SMILES): N#CCNC(=O)Cc1nnc(Cc2nc3c(Br)cccc3s2)o1
InChIKey: QAVOTORXYKURIZ-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 392.24, ALogP 2.21, HBA 7, HBD 1, PSA 104.7, QED 0.67
Compound (SMILES): N#CCNC(=O)Cc1nnc(Cc2nc3c(-c4ccccc4)cccc3s2)o1
InChIKey: MMAIVBOTPCLDBQ-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 389.44, ALogP 3.12, HBA 7, HBD 1, PSA 104.7, QED 0.51
Compound (SMILES): Cn1ccc(-c2ccc3nc(Cc4nnc(CC(=O)NC5(C#N)CC5)o4)sc3c2)n1
InChIKey: VJCSICSRIRFELP-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 419.47, ALogP 2.39, HBA 9, HBD 1, PSA 122.52, QED 0.51
Compound (SMILES): N#CCNC(=O)Cc1nnc(Cc2ccc3cc(-c4ccccc4)ccc3n2)o1
InChIKey: VTBKRCLWEFLCOW-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 383.41, ALogP 3.06, HBA 6, HBD 1, PSA 104.7, QED 0.51
Compound (SMILES): N#CCNC(=O)Cc1nnc(Cc2cnc3cc(-c4ccccc4)ccc3n2)o1
InChIKey: PKQQUFXPSWZLGG-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 384.4, ALogP 2.45, HBA 7, HBD 1, PSA 117.59, QED 0.51
Compound (SMILES): N#CCNC(=O)Cc1nnc(Cc2ccc(-c3ccccc3)cn2)o1
InChIKey: DURBCUGVYTUWEM-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 23000 nM (pChEMBL 4.639999866485596)
Descriptors: MW 333.35, ALogP 1.9, HBA 6, HBD 1, PSA 104.7, QED 0.69
Compound (SMILES): Cn1cc(-c2ccc3sc(Cc4nnc(CC(=O)NC5(C#N)CC5)o4)nc3c2)cn1
InChIKey: XGIFOCZIFOTCPD-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 419.47, ALogP 2.39, HBA 9, HBD 1, PSA 122.52, QED 0.51
Compound (SMILES): O=C(Cc1nnc(Cc2nc3ccc(-c4ccc(F)cc4)cc3s2)o1)NC1(CO)CC1
InChIKey: QYLQPAPRRTUDQS-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 438.48, ALogP 3.26, HBA 7, HBD 2, PSA 101.14, QED 0.46
Compound (SMILES): N#CC1(NC(=O)Cc2nnc(Cc3nc4c(-c5ccccc5)cccc4s3)o2)CC1
InChIKey: OBDGLUFCKUCTHP-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 415.48, ALogP 3.65, HBA 7, HBD 1, PSA 104.7, QED 0.52
Compound (SMILES): O=C(Cc1nnc(Cc2nc3c(-c4ccccc4)cccc3s2)o1)NC1(CO)CC1
InChIKey: NXWRLOPNPVQPLV-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 420.49, ALogP 3.12, HBA 7, HBD 2, PSA 101.14, QED 0.48
Compound (SMILES): N#CCNC(=O)Cc1nnc(C(F)(F)c2nc3ccc(-c4ccccc4)cc3s2)o1
InChIKey: IDHFHRNBKVJFGG-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 425.42, ALogP 3.67, HBA 7, HBD 1, PSA 104.7, QED 0.47
Compound (SMILES): O=C(Cc1nnc(Cc2nc3ccc(-c4ccccc4)cc3s2)o1)N1CC(O)C1
InChIKey: UXRKNEYUOTUZCU-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 406.47, ALogP 2.68, HBA 7, HBD 1, PSA 92.35, QED 0.55
Compound (SMILES): O=C(Cc1nnc(Cc2nc3ccc(-c4ccccc4)cc3s2)o1)NC1COC1
InChIKey: CEVUNHOJWJSUGS-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 406.47, ALogP 2.99, HBA 7, HBD 1, PSA 90.14, QED 0.53
Compound (SMILES): CC(C#N)NC(=O)Cc1nnc(Cc2nc3ccc(-c4ccccc4)cc3s2)o1
InChIKey: FUSHUKYXXFTOQV-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 403.47, ALogP 3.51, HBA 7, HBD 1, PSA 104.7, QED 0.53
Compound (SMILES): N#CC1(NC(=O)Cc2nnc(Cc3nc4ccc(Cc5ccc(F)cc5)cc4s3)o2)CC1
InChIKey: ZIKFULFBFKYEAL-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 447.5, ALogP 3.71, HBA 7, HBD 1, PSA 104.7, QED 0.46
Compound (SMILES): N#CC1(NC(=O)Cc2nnc(Cc3nc4ccc(C5=CCOCC5)cc4s3)o2)CC1
InChIKey: NWBCIHPRDVLWLS-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 421.48, ALogP 2.79, HBA 8, HBD 1, PSA 113.93, QED 0.65
Compound (SMILES): N#CC1(NC(=O)Cc2nnc(Cc3nc4ccc(-c5ccc(Cl)s5)cc4s3)o2)CC1
InChIKey: CLEKXRTUWQTFLM-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 455.95, ALogP 4.37, HBA 8, HBD 1, PSA 104.7, QED 0.46
Compound (SMILES): N#CC1(NC(=O)Cc2nnc(Cc3nc4ccc(-c5cc6ccccc6s5)cc4s3)o2)CC1
InChIKey: QZTJAMVYRXZOON-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 471.57, ALogP 4.87, HBA 8, HBD 1, PSA 104.7, QED 0.38
Compound (SMILES): N#CC1(NC(=O)Cc2nnc(Cc3nc4ccc(-c5ncc(F)cn5)cc4s3)o2)CC1
InChIKey: LMZOKJRPOYRKNC-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition Assay: After the present compound dissolved in DMSO was added to become 0.5% DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added (total volume was 20 μl). After 4-hour reaction at 37 C., non-esterified fatty acid (NEFA) generated from HDL by EL was measured with a commercially available assay kit and the amount of NEFA was used as an index of enzyme activity. Considering the enzyme activity without the inhibitor as a control value, the inhibition rate of each concentration of the present compound was calculated, and 50% inhibitory concentration (IC50 value) was calculated from an inhibition curve.
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 435.44, ALogP 2.58, HBA 9, HBD 1, PSA 130.48, QED 0.49