lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCN(C)C1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2S1
InChIKey: ZYLZEOISGVWISQ-VVULQXIFSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition Assay: Enzymatic reactions were carried out in a reaction containing 50 mM NaH2PO4, 100 mM NaCl and 0.1% BSA (pH 7.0) using 2 mM 4-Methylumbelliferyl N-acetyl-β-D-glucosaminide dihydrate (Sigma M2133) dissolved in ddH2O, as a substrate. The amount of purified human O-GlcNAcase enzyme used in the reaction was 0.7 nM. Test compound of varying concentrations was added to the enzyme prior to initiation of the reaction. The reaction was performed at room temperature in a 96-well plate and was initiated with the addition of substrate. The production of fluorescent product was measured every 60 sec for 45 min with a Tecan Infinite M200 plate-reader with excitation at 355 nM and emission detected at 460 nM, with 4-Methylumbelliferone (Sigma M1381) used to produce a standard curve. The slope of product production was determined for each concentration of compound tested and plotted, using standard curve fitting algorithms for sigmoidal dose response curves.
Measurement: Ki = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 276.36, ALogP -0.76, HBA 7, HBD 3, PSA 85.52, QED 0.63
Compound (SMILES): C=CCN(C)C1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2S1
InChIKey: LWUCOZJHZOPZGY-VVULQXIFSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition Assay: Enzymatic reactions were carried out in a reaction containing 50 mM NaH2PO4, 100 mM NaCl and 0.1% BSA (pH 7.0) using 2 mM 4-Methylumbelliferyl N-acetyl-β-D-glucosaminide dihydrate (Sigma M2133) dissolved in ddH2O, as a substrate. The amount of purified human O-GlcNAcase enzyme used in the reaction was 0.7 nM. Test compound of varying concentrations was added to the enzyme prior to initiation of the reaction. The reaction was performed at room temperature in a 96-well plate and was initiated with the addition of substrate. The production of fluorescent product was measured every 60 sec for 45 min with a Tecan Infinite M200 plate-reader with excitation at 355 nM and emission detected at 460 nM, with 4-Methylumbelliferone (Sigma M1381) used to produce a standard curve. The slope of product production was determined for each concentration of compound tested and plotted, using standard curve fitting algorithms for sigmoidal dose response curves.
Measurement: Ki = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 274.34, ALogP -0.99, HBA 7, HBD 3, PSA 85.52, QED 0.57
Compound (SMILES): CON(C)C1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2S1
InChIKey: QHGGQSRRRSUEST-FMDGEEDCSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition Assay: Enzymatic reactions were carried out in a reaction containing 50 mM NaH2PO4, 100 mM NaCl and 0.1% BSA (pH 7.0) using 2 mM 4-Methylumbelliferyl N-acetyl-β-D-glucosaminide dihydrate (Sigma M2133) dissolved in ddH2O, as a substrate. The amount of purified human O-GlcNAcase enzyme used in the reaction was 0.7 nM. Test compound of varying concentrations was added to the enzyme prior to initiation of the reaction. The reaction was performed at room temperature in a 96-well plate and was initiated with the addition of substrate. The production of fluorescent product was measured every 60 sec for 45 min with a Tecan Infinite M200 plate-reader with excitation at 355 nM and emission detected at 460 nM, with 4-Methylumbelliferone (Sigma M1381) used to produce a standard curve. The slope of product production was determined for each concentration of compound tested and plotted, using standard curve fitting algorithms for sigmoidal dose response curves.
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 264.3, ALogP -1.61, HBA 8, HBD 3, PSA 94.75, QED 0.52
Compound (SMILES): CCC(=O)NC1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2S1
InChIKey: WJYOPIDXDSUXAT-GPMKSPRZSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition Assay: Enzymatic reactions were carried out in a reaction containing 50 mM NaH2PO4, 100 mM NaCl and 0.1% BSA (pH 7.0) using 2 mM 4-Methylumbelliferyl N-acetyl-β-D-glucosaminide dihydrate (Sigma M2133) dissolved in ddH2O, as a substrate. The amount of purified human O-GlcNAcase enzyme used in the reaction was 0.7 nM. Test compound of varying concentrations was added to the enzyme prior to initiation of the reaction. The reaction was performed at room temperature in a 96-well plate and was initiated with the addition of substrate. The production of fluorescent product was measured every 60 sec for 45 min with a Tecan Infinite M200 plate-reader with excitation at 355 nM and emission detected at 460 nM, with 4-Methylumbelliferone (Sigma M1381) used to produce a standard curve. The slope of product production was determined for each concentration of compound tested and plotted, using standard curve fitting algorithms for sigmoidal dose response curves.
Measurement: Ki = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 276.31, ALogP -1.58, HBA 7, HBD 4, PSA 111.38, QED 0.48
Compound (SMILES): CCNC(=O)NC1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2S1
InChIKey: YGUXOQPKTZITMG-FMDGEEDCSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition Assay: Enzymatic reactions were carried out in a reaction containing 50 mM NaH2PO4, 100 mM NaCl and 0.1% BSA (pH 7.0) using 2 mM 4-Methylumbelliferyl N-acetyl-β-D-glucosaminide dihydrate (Sigma M2133) dissolved in ddH2O, as a substrate. The amount of purified human O-GlcNAcase enzyme used in the reaction was 0.7 nM. Test compound of varying concentrations was added to the enzyme prior to initiation of the reaction. The reaction was performed at room temperature in a 96-well plate and was initiated with the addition of substrate. The production of fluorescent product was measured every 60 sec for 45 min with a Tecan Infinite M200 plate-reader with excitation at 355 nM and emission detected at 460 nM, with 4-Methylumbelliferone (Sigma M1381) used to produce a standard curve. The slope of product production was determined for each concentration of compound tested and plotted, using standard curve fitting algorithms for sigmoidal dose response curves.
Measurement: Ki = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 291.33, ALogP -1.78, HBA 7, HBD 5, PSA 123.41, QED 0.41
Compound (SMILES): NC[C@H]1O[C@@H](n2c(SCC(=O)NC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@@H](O)C3O)nc3c(N)ncnc32)[C@@H](O)C1O
InChIKey: LQEPCCOATFPPEE-JXMPDTSMSA-N
Target: NAD kinase (SINGLE PROTEIN), Staphylococcus aureus (strain COL)
UniProt: Q5HH78
Assay: Inhibitor Assay: For inhibitor assays, IC50 was determined, in the presence of 1 mM NAD and 4 mM ATP (for LmNADK1) or 2 mM ATP (for SaNADK). Dixon plots were used to determine KI in the presence of 4 mM ATP (for LmNADK11) or 2 mM ATP (for Sa NADK) and three NAD concentrations (0.2, 0.5 and 1 mM). It was also checked that the inhibitors had no effect on the coupling enzyme activity.
Measurement: Ki = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 604.61, ALogP -3.76, HBA 19, HBD 8, PSA 293.74, QED 0.09
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](CNCC#Cc2nc3c(N)ncnc3n2[C@@H]2O[C@H](CO)C(O)[C@@H]2O)C(O)[C@@H]1O
InChIKey: CGSYXPCXDPYUKS-WCWPUKFQSA-N
Target: NAD kinase 1 (SINGLE PROTEIN), Listeria monocytogenes serotype 4b (strain F2365)
UniProt: Q721J8
Assay: Inhibitor Assay: For inhibitor assays, IC50 was determined, in the presence of 1 mM NAD and 4 mM ATP (for LmNADK1) or 2 mM ATP (for SaNADK). Dixon plots were used to determine KI in the presence of 4 mM ATP (for LmNADK11) or 2 mM ATP (for Sa NADK) and three NAD concentrations (0.2, 0.5 and 1 mM). It was also checked that the inhibitors had no effect on the coupling enzyme activity.
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 569.54, ALogP -4, HBA 18, HBD 8, PSA 270.88, QED 0.08
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](COCC#Cc2nc3c(N)ncnc3n2[C@@H]2O[C@H](CO)C(O)[C@@H]2O)C(O)[C@@H]1O
InChIKey: DDNDMZZNOIOKKS-WCWPUKFQSA-N
Target: NAD kinase 1 (SINGLE PROTEIN), Listeria monocytogenes serotype 4b (strain F2365)
UniProt: Q721J8
Assay: Inhibitor Assay: For inhibitor assays, IC50 was determined, in the presence of 1 mM NAD and 4 mM ATP (for LmNADK1) or 2 mM ATP (for SaNADK). Dixon plots were used to determine KI in the presence of 4 mM ATP (for LmNADK11) or 2 mM ATP (for Sa NADK) and three NAD concentrations (0.2, 0.5 and 1 mM). It was also checked that the inhibitors had no effect on the coupling enzyme activity.
Measurement: Ki = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 570.52, ALogP -3.57, HBA 18, HBD 7, PSA 268.08, QED 0.09
Compound (SMILES): Cc1cc(C)c(C(=O)NC(Cc2ccc(N3CC(CNc4ccccn4)C3)cc2)C(=O)O)c(C)c1
InChIKey: QVTCVZDZHPJPIH-UHFFFAOYSA-N
Target: Integrin alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08648
Assay: Binding Assay: Fibronectin was diluted with coating buffer (15 mM Na2CO3, 35 mM NaHCO3, pH 9.6) and coated with 100 uL/well to Nunc-Immuno maxisorp plates (Nalge Nunc Europe Ltd) over night at 4 C. After discarding the coating solution plates were washed 3 times with buffer 1 (25 mM Tris, pH 7.6, 150 mM NaCl, 1 mM MnCl2, 1 mg/ml BSA) and blocked with 100 uL blocking buffer (3% BSA in PBS 0.1% Tween20) for 1 hour at room temperature. After washing the blocked plates (3 times) with buffer 1, integrin (50 uL) and either inhibitor (serial dilution in buffer 1) or buffer 1 (50 uL) were added to the wells and incubated for one hour at RT. Plates were then washed (3 times) with buffer 1 and incubated with 100 uL of anti-human-Fc-HRP antibody conjugate (Sigma-Aldrich, Taufkirchen, Germany) in buffer 1 for 1 hour at RT. After additional washing steps (3 times) with buffer 150 uL of HRP substrate solution TMB (Seramun, Germany) were added to the wells.
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 472.59, ALogP 3.98, HBA 5, HBD 3, PSA 94.56, QED 0.44
Compound (SMILES): Cc1ccnc(NCC2CC(=O)N(c3ccc(CC(NC(=O)c4c(C)cc(C)cc4C)C(=O)O)cc3)C2)c1
InChIKey: UEBUMZGZKUPTHB-UHFFFAOYSA-N
Target: Integrin alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08648
Assay: Binding Assay: Fibronectin was diluted with coating buffer (15 mM Na2CO3, 35 mM NaHCO3, pH 9.6) and coated with 100 uL/well to Nunc-Immuno maxisorp plates (Nalge Nunc Europe Ltd) over night at 4 C. After discarding the coating solution plates were washed 3 times with buffer 1 (25 mM Tris, pH 7.6, 150 mM NaCl, 1 mM MnCl2, 1 mg/ml BSA) and blocked with 100 uL blocking buffer (3% BSA in PBS 0.1% Tween20) for 1 hour at room temperature. After washing the blocked plates (3 times) with buffer 1, integrin (50 uL) and either inhibitor (serial dilution in buffer 1) or buffer 1 (50 uL) were added to the wells and incubated for one hour at RT. Plates were then washed (3 times) with buffer 1 and incubated with 100 uL of anti-human-Fc-HRP antibody conjugate (Sigma-Aldrich, Taufkirchen, Germany) in buffer 1 for 1 hour at RT. After additional washing steps (3 times) with buffer 150 uL of HRP substrate solution TMB (Seramun, Germany) were added to the wells.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 514.63, ALogP 4.21, HBA 5, HBD 3, PSA 111.63, QED 0.39
Compound (SMILES): Cc1cc(C)c(C(=O)NC(Cc2ccc(N3CCC(CNc4nc5ccccc5[nH]4)CC3)cc2)C(=O)O)c(C)c1
InChIKey: CJQBRSWCDQZXGS-UHFFFAOYSA-N
Target: Integrin alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08648
Assay: Binding Assay: Fibronectin was diluted with coating buffer (15 mM Na2CO3, 35 mM NaHCO3, pH 9.6) and coated with 100 uL/well to Nunc-Immuno maxisorp plates (Nalge Nunc Europe Ltd) over night at 4 C. After discarding the coating solution plates were washed 3 times with buffer 1 (25 mM Tris, pH 7.6, 150 mM NaCl, 1 mM MnCl2, 1 mg/ml BSA) and blocked with 100 uL blocking buffer (3% BSA in PBS 0.1% Tween20) for 1 hour at room temperature. After washing the blocked plates (3 times) with buffer 1, integrin (50 uL) and either inhibitor (serial dilution in buffer 1) or buffer 1 (50 uL) were added to the wells and incubated for one hour at RT. Plates were then washed (3 times) with buffer 1 and incubated with 100 uL of anti-human-Fc-HRP antibody conjugate (Sigma-Aldrich, Taufkirchen, Germany) in buffer 1 for 1 hour at RT. After additional washing steps (3 times) with buffer 150 uL of HRP substrate solution TMB (Seramun, Germany) were added to the wells.
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 539.68, ALogP 5.24, HBA 5, HBD 4, PSA 110.35, QED 0.23
Compound (SMILES): Cc1cc(C)c(C(=O)NC(Cc2ccc(N3CCC(c4ccc5c(n4)NCCC5)CC3)cc2)C(=O)O)c(C)c1
InChIKey: RWENQEHCTSXFGI-UHFFFAOYSA-N
Target: Integrin alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08648
Assay: Binding Assay: Fibronectin was diluted with coating buffer (15 mM Na2CO3, 35 mM NaHCO3, pH 9.6) and coated with 100 uL/well to Nunc-Immuno maxisorp plates (Nalge Nunc Europe Ltd) over night at 4 C. After discarding the coating solution plates were washed 3 times with buffer 1 (25 mM Tris, pH 7.6, 150 mM NaCl, 1 mM MnCl2, 1 mg/ml BSA) and blocked with 100 uL blocking buffer (3% BSA in PBS 0.1% Tween20) for 1 hour at room temperature. After washing the blocked plates (3 times) with buffer 1, integrin (50 uL) and either inhibitor (serial dilution in buffer 1) or buffer 1 (50 uL) were added to the wells and incubated for one hour at RT. Plates were then washed (3 times) with buffer 1 and incubated with 100 uL of anti-human-Fc-HRP antibody conjugate (Sigma-Aldrich, Taufkirchen, Germany) in buffer 1 for 1 hour at RT. After additional washing steps (3 times) with buffer 150 uL of HRP substrate solution TMB (Seramun, Germany) were added to the wells.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 526.68, ALogP 5.17, HBA 5, HBD 3, PSA 94.56, QED 0.39
Compound (SMILES): CC1(C(=O)NC(CC2CCN(C(=O)CCc3ccc4c(n3)NCCC4)CC2)C(=O)O)CCCCC1
InChIKey: BQIRKRXYFAKFJD-UHFFFAOYSA-N
Target: Integrin alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08648
Assay: Binding Assay: Fibronectin was diluted with coating buffer (15 mM Na2CO3, 35 mM NaHCO3, pH 9.6) and coated with 100 uL/well to Nunc-Immuno maxisorp plates (Nalge Nunc Europe Ltd) over night at 4 C. After discarding the coating solution plates were washed 3 times with buffer 1 (25 mM Tris, pH 7.6, 150 mM NaCl, 1 mM MnCl2, 1 mg/ml BSA) and blocked with 100 uL blocking buffer (3% BSA in PBS 0.1% Tween20) for 1 hour at room temperature. After washing the blocked plates (3 times) with buffer 1, integrin (50 uL) and either inhibitor (serial dilution in buffer 1) or buffer 1 (50 uL) were added to the wells and incubated for one hour at RT. Plates were then washed (3 times) with buffer 1 and incubated with 100 uL of anti-human-Fc-HRP antibody conjugate (Sigma-Aldrich, Taufkirchen, Germany) in buffer 1 for 1 hour at RT. After additional washing steps (3 times) with buffer 150 uL of HRP substrate solution TMB (Seramun, Germany) were added to the wells.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 484.64, ALogP 3.54, HBA 5, HBD 3, PSA 111.63, QED 0.52
Compound (SMILES): Cc1ccnc(NCC2CCN(c3ccc(CC(NC(=O)C4(C)CCCCC4)C(=O)O)cc3)CC2)c1
InChIKey: LPVSLEMCWYULHS-UHFFFAOYSA-N
Target: Integrin alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08648
Assay: Binding Assay: Fibronectin was diluted with coating buffer (15 mM Na2CO3, 35 mM NaHCO3, pH 9.6) and coated with 100 uL/well to Nunc-Immuno maxisorp plates (Nalge Nunc Europe Ltd) over night at 4 C. After discarding the coating solution plates were washed 3 times with buffer 1 (25 mM Tris, pH 7.6, 150 mM NaCl, 1 mM MnCl2, 1 mg/ml BSA) and blocked with 100 uL blocking buffer (3% BSA in PBS 0.1% Tween20) for 1 hour at room temperature. After washing the blocked plates (3 times) with buffer 1, integrin (50 uL) and either inhibitor (serial dilution in buffer 1) or buffer 1 (50 uL) were added to the wells and incubated for one hour at RT. Plates were then washed (3 times) with buffer 1 and incubated with 100 uL of anti-human-Fc-HRP antibody conjugate (Sigma-Aldrich, Taufkirchen, Germany) in buffer 1 for 1 hour at RT. After additional washing steps (3 times) with buffer 150 uL of HRP substrate solution TMB (Seramun, Germany) were added to the wells.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 492.66, ALogP 4.8, HBA 5, HBD 3, PSA 94.56, QED 0.47
Compound (SMILES): Cc1ccnc(NCC2CCN(c3ccc(CC(NC(=O)c4ccccc4)C(=O)O)cc3)CC2)c1
InChIKey: RYVSEJYVROGWSK-UHFFFAOYSA-N
Target: Integrin alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08648
Assay: Binding Assay: Fibronectin was diluted with coating buffer (15 mM Na2CO3, 35 mM NaHCO3, pH 9.6) and coated with 100 uL/well to Nunc-Immuno maxisorp plates (Nalge Nunc Europe Ltd) over night at 4 C. After discarding the coating solution plates were washed 3 times with buffer 1 (25 mM Tris, pH 7.6, 150 mM NaCl, 1 mM MnCl2, 1 mg/ml BSA) and blocked with 100 uL blocking buffer (3% BSA in PBS 0.1% Tween20) for 1 hour at room temperature. After washing the blocked plates (3 times) with buffer 1, integrin (50 uL) and either inhibitor (serial dilution in buffer 1) or buffer 1 (50 uL) were added to the wells and incubated for one hour at RT. Plates were then washed (3 times) with buffer 1 and incubated with 100 uL of anti-human-Fc-HRP antibody conjugate (Sigma-Aldrich, Taufkirchen, Germany) in buffer 1 for 1 hour at RT. After additional washing steps (3 times) with buffer 150 uL of HRP substrate solution TMB (Seramun, Germany) were added to the wells.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 472.59, ALogP 4.14, HBA 5, HBD 3, PSA 94.56, QED 0.43
Compound (SMILES): Cc1ccnc(NCC2CCN(c3ccc(CC(NC(=O)C(c4ccccc4)C(C)C)C(=O)O)cc3)CC2)c1
InChIKey: KDLIPUJWJZDKHQ-UHFFFAOYSA-N
Target: Integrin alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08648
Assay: Binding Assay: Fibronectin was diluted with coating buffer (15 mM Na2CO3, 35 mM NaHCO3, pH 9.6) and coated with 100 uL/well to Nunc-Immuno maxisorp plates (Nalge Nunc Europe Ltd) over night at 4 C. After discarding the coating solution plates were washed 3 times with buffer 1 (25 mM Tris, pH 7.6, 150 mM NaCl, 1 mM MnCl2, 1 mg/ml BSA) and blocked with 100 uL blocking buffer (3% BSA in PBS 0.1% Tween20) for 1 hour at room temperature. After washing the blocked plates (3 times) with buffer 1, integrin (50 uL) and either inhibitor (serial dilution in buffer 1) or buffer 1 (50 uL) were added to the wells and incubated for one hour at RT. Plates were then washed (3 times) with buffer 1 and incubated with 100 uL of anti-human-Fc-HRP antibody conjugate (Sigma-Aldrich, Taufkirchen, Germany) in buffer 1 for 1 hour at RT. After additional washing steps (3 times) with buffer 150 uL of HRP substrate solution TMB (Seramun, Germany) were added to the wells.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 528.7, ALogP 5.27, HBA 5, HBD 3, PSA 94.56, QED 0.31
Compound (SMILES): CCCNC(=O)NCC1CCN(c2ccc(CC(NC(=O)c3c(C)cc(C)cc3C)C(=O)O)cc2)CC1
InChIKey: RYXMTPQVVCXGQU-UHFFFAOYSA-N
Target: Integrin alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08648
Assay: Binding Assay: Fibronectin was diluted with coating buffer (15 mM Na2CO3, 35 mM NaHCO3, pH 9.6) and coated with 100 uL/well to Nunc-Immuno maxisorp plates (Nalge Nunc Europe Ltd) over night at 4 C. After discarding the coating solution plates were washed 3 times with buffer 1 (25 mM Tris, pH 7.6, 150 mM NaCl, 1 mM MnCl2, 1 mg/ml BSA) and blocked with 100 uL blocking buffer (3% BSA in PBS 0.1% Tween20) for 1 hour at room temperature. After washing the blocked plates (3 times) with buffer 1, integrin (50 uL) and either inhibitor (serial dilution in buffer 1) or buffer 1 (50 uL) were added to the wells and incubated for one hour at RT. Plates were then washed (3 times) with buffer 1 and incubated with 100 uL of anti-human-Fc-HRP antibody conjugate (Sigma-Aldrich, Taufkirchen, Germany) in buffer 1 for 1 hour at RT. After additional washing steps (3 times) with buffer 150 uL of HRP substrate solution TMB (Seramun, Germany) were added to the wells.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 508.66, ALogP 3.96, HBA 4, HBD 4, PSA 110.77, QED 0.39
Compound (SMILES): CC1(CO)Cc2nnc(C3(c4ccc(-c5ccccc5)cc4)CC3)n2CCS1
InChIKey: KJIBRMRRCCDONN-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 391.54, ALogP 4.07, HBA 5, HBD 1, PSA 50.94, QED 0.73
Compound (SMILES): CC1(CO)Cc2nnc(C3(c4ccc(-c5cccnc5)cc4)CC3)n2CCS1
InChIKey: RCJRSUJOPLWBPI-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 392.53, ALogP 3.46, HBA 6, HBD 1, PSA 63.83, QED 0.74
Compound (SMILES): C[C@@]1(CO)Cc2nnc(C3(c4ccc(-c5cccnc5)cc4)CC3)n2CCS1
InChIKey: RCJRSUJOPLWBPI-NRFANRHFSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 392.53, ALogP 3.46, HBA 6, HBD 1, PSA 63.83, QED 0.74
Compound (SMILES): C[C@]1(CO)Cc2nnc(C3(c4ccc(-c5cccnc5)cc4)CC3)n2CCS1
InChIKey: RCJRSUJOPLWBPI-OAQYLSRUSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 392.53, ALogP 3.46, HBA 6, HBD 1, PSA 63.83, QED 0.74
Compound (SMILES): CN(C)C(=O)c1ccc(-c2ccc(C3(c4nnc5n4CCSC(C)(CO)C5)CC3)cc2)cc1
InChIKey: WPOVXVHQWWEKNU-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 462.62, ALogP 3.77, HBA 6, HBD 1, PSA 71.25, QED 0.63
Compound (SMILES): CN(C)C(=O)c1cccc(-c2ccc(C3(c4nnc5n4CCSC(C)(CO)C5)CC3)cc2)c1
InChIKey: OXUVTRYNINSHMU-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 462.62, ALogP 3.77, HBA 6, HBD 1, PSA 71.25, QED 0.63
Compound (SMILES): CC1(CO)Cc2nnc(C3(c4ccc(-c5cccnc5)c(F)c4)CC3)n2CCS1
InChIKey: INJNKRDXNHYXPE-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 410.52, ALogP 3.6, HBA 6, HBD 1, PSA 63.83, QED 0.71
Compound (SMILES): Cn1cc(-c2ccc(C3(c4nnc5n4CCSC(C)(CO)C5)CC3)cc2)cn1
InChIKey: PTXJDKXORGVEGX-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 395.53, ALogP 2.8, HBA 7, HBD 1, PSA 68.76, QED 0.74
Compound (SMILES): Cn1cc(-c2ccc(C3(c4nnc5n4CCS[C@@](C)(CO)C5)CC3)cc2)cn1
InChIKey: PTXJDKXORGVEGX-HXUWFJFHSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 395.53, ALogP 2.8, HBA 7, HBD 1, PSA 68.76, QED 0.74
Compound (SMILES): CN(C)C(=O)c1ccc(-c2ccc(C3(c4nnc5n4CCSC(C)(CO)C5)CC3)cc2)nc1
InChIKey: KPMABPBYWGSJAL-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 463.61, ALogP 3.16, HBA 7, HBD 1, PSA 84.14, QED 0.63
Compound (SMILES): CN(C)C(=O)c1ccc(-c2ccc(C3(c4nnc5n4CCS[C@@](C)(CO)C5)CC3)cc2)nc1
InChIKey: KPMABPBYWGSJAL-XMMPIXPASA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 463.61, ALogP 3.16, HBA 7, HBD 1, PSA 84.14, QED 0.63
Compound (SMILES): Cn1cc(-c2ccc(C3(c4nnc5n4CCS[C@@](C)(CO)C5)CC3)c(F)c2)cn1
InChIKey: JHTNCJQJLDQSEO-HXUWFJFHSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 413.52, ALogP 2.94, HBA 7, HBD 1, PSA 68.76, QED 0.71
Compound (SMILES): Cc1ncc(-c2ccc(C3(c4nnc5n4CCS[C@@](C)(CO)C5)CC3)cc2)cn1
InChIKey: MNUMPHVYCBNPLG-OAQYLSRUSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 407.54, ALogP 3.16, HBA 7, HBD 1, PSA 76.72, QED 0.72
Compound (SMILES): Cc1ccc(-c2ccc(C3(c4nnc5n4CCS[C@@](C)(CO)C5)CC3)c(F)c2)nn1
InChIKey: ABSVLPXNRBAQSC-OAQYLSRUSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Enzyme Inhibition Assay: A reaction was performed on a 384-well plate (Greiner Bio One) using a reaction volume of 24 µL, and all the samples were diluted with an assay buffer (50 mM tris buffer, pH 7.4, 10% glycerol). 0.8 mM NADPH, 6 mM glucose 6-phosphate, 0.35 units/mL glucose 6-phosphate dehydrogenase (Sigma Chemical), and 3 mM magnesium chloride and a microsome fraction as an enzyme source were added to the plate, and a solution containing a test compound dissolved in a dimethyl sulfoxide/methanol solution was added at a final concentration of 0.1%. After the addition of the test compound, cortisone at a final concentration of 160 nM was added to start the reaction, and the reaction was performed at room temperature for 3 h. 25 µL of 100 mM carbenoxolone (Sigma Chemical) was added to terminate the reaction, and the amount of cortisol produced was measured with RUBYstar (BMG LABTECH JAPAN Ltd.) using a cortisol prototype kit (Cisbio International) according to the package insert.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 425.53, ALogP 3.3, HBA 7, HBD 1, PSA 76.72, QED 0.69
Compound (SMILES): CC(C)(O)CC1(c2ccccc2)CCN(C(C)(C)C#Cc2ccc(F)cc2)C(=O)O1
InChIKey: ARKIMVVPWZUORY-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Scintillation Proximity Assay: The inhibition of a microsomal preparation of 11beta -HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384). All reactions were carried out at rt in 96 well clear flexible PET Microbeta plates (PerkinElmer). The assay begins by dispensing 49 ul of substrate solution (50 mM HEPES, pH 7.4, 100 mM KCl, 5 mM NaCl, 2 mM MgCl2, 2 mM NADPH and 160 nM [3H]cortisone (1 Ci/mmol)) and mixing in 1 uL of the test compounds in DMSO previously diluted in half-log increments (8 points) starting at 0.1 mM. After a 10 minute pre-incubation, 50 uL of enzyme solution containing microsomes isolated from CHO cells overexpressing human 11beta -HSD1 (10-20 ug/ml of total protein) was added.
Measurement: IC50 = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 409.5, ALogP 4.85, HBA 3, HBD 1, PSA 49.77, QED 0.73
Compound (SMILES): C=C(C)CC1(c2ccccc2)CCN(C(C)(C)C#Cc2ccc3c(ccc(=O)n3C)c2)C(=O)O1
InChIKey: CDCBSFVLVTUBBD-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Scintillation Proximity Assay: The inhibition of a microsomal preparation of 11beta -HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384). All reactions were carried out at rt in 96 well clear flexible PET Microbeta plates (PerkinElmer). The assay begins by dispensing 49 ul of substrate solution (50 mM HEPES, pH 7.4, 100 mM KCl, 5 mM NaCl, 2 mM MgCl2, 2 mM NADPH and 160 nM [3H]cortisone (1 Ci/mmol)) and mixing in 1 uL of the test compounds in DMSO previously diluted in half-log increments (8 points) starting at 0.1 mM. After a 10 minute pre-incubation, 50 uL of enzyme solution containing microsomes isolated from CHO cells overexpressing human 11beta -HSD1 (10-20 ug/ml of total protein) was added.
Measurement: IC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 454.57, ALogP 5.37, HBA 4, HBD 0, PSA 51.54, QED 0.39
Compound (SMILES): CC(C)(C)CC1(c2ccccc2)CCN(C(C)(C)c2cn(-c3ccccc3)nn2)C(=O)O1
InChIKey: YKECSXDVYXEQDN-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Scintillation Proximity Assay: The inhibition of a microsomal preparation of 11beta -HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384). All reactions were carried out at rt in 96 well clear flexible PET Microbeta plates (PerkinElmer). The assay begins by dispensing 49 ul of substrate solution (50 mM HEPES, pH 7.4, 100 mM KCl, 5 mM NaCl, 2 mM MgCl2, 2 mM NADPH and 160 nM [3H]cortisone (1 Ci/mmol)) and mixing in 1 uL of the test compounds in DMSO previously diluted in half-log increments (8 points) starting at 0.1 mM. After a 10 minute pre-incubation, 50 uL of enzyme solution containing microsomes isolated from CHO cells overexpressing human 11beta -HSD1 (10-20 ug/ml of total protein) was added.
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 432.57, ALogP 5.68, HBA 5, HBD 0, PSA 60.25, QED 0.52
Compound (SMILES): Cn1ccc(-c2ccc(C3(N4CCC(CC(C)(C)O)(c5ccccc5)OC4=O)CC3)cc2)cc1=O
InChIKey: VFTUQILKPMQCDB-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Scintillation Proximity Assay: The inhibition of a microsomal preparation of 11beta -HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384). All reactions were carried out at rt in 96 well clear flexible PET Microbeta plates (PerkinElmer). The assay begins by dispensing 49 ul of substrate solution (50 mM HEPES, pH 7.4, 100 mM KCl, 5 mM NaCl, 2 mM MgCl2, 2 mM NADPH and 160 nM [3H]cortisone (1 Ci/mmol)) and mixing in 1 uL of the test compounds in DMSO previously diluted in half-log increments (8 points) starting at 0.1 mM. After a 10 minute pre-incubation, 50 uL of enzyme solution containing microsomes isolated from CHO cells overexpressing human 11beta -HSD1 (10-20 ug/ml of total protein) was added.
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 472.59, ALogP 4.94, HBA 5, HBD 1, PSA 71.77, QED 0.55
Compound (SMILES): CC(C)(O)CC1(c2ccccc2)CCN(C(C)(C)c2ccc(Br)cc2)C(=O)O1
InChIKey: KMVPGLZAXSHKHE-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Scintillation Proximity Assay: The inhibition of a microsomal preparation of 11beta -HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384). All reactions were carried out at rt in 96 well clear flexible PET Microbeta plates (PerkinElmer). The assay begins by dispensing 49 ul of substrate solution (50 mM HEPES, pH 7.4, 100 mM KCl, 5 mM NaCl, 2 mM MgCl2, 2 mM NADPH and 160 nM [3H]cortisone (1 Ci/mmol)) and mixing in 1 uL of the test compounds in DMSO previously diluted in half-log increments (8 points) starting at 0.1 mM. After a 10 minute pre-incubation, 50 uL of enzyme solution containing microsomes isolated from CHO cells overexpressing human 11beta -HSD1 (10-20 ug/ml of total protein) was added.
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 446.39, ALogP 5.58, HBA 3, HBD 1, PSA 49.77, QED 0.65
Compound (SMILES): C=C(C)CC1(c2ccccc2)CCN(C(C)(C)C#Cc2ccc(F)cc2)C(=O)O1
InChIKey: XPXQTBUMBSVDNW-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Scintillation Proximity Assay: The inhibition of a microsomal preparation of 11beta -HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384). All reactions were carried out at rt in 96 well clear flexible PET Microbeta plates (PerkinElmer). The assay begins by dispensing 49 ul of substrate solution (50 mM HEPES, pH 7.4, 100 mM KCl, 5 mM NaCl, 2 mM MgCl2, 2 mM NADPH and 160 nM [3H]cortisone (1 Ci/mmol)) and mixing in 1 uL of the test compounds in DMSO previously diluted in half-log increments (8 points) starting at 0.1 mM. After a 10 minute pre-incubation, 50 uL of enzyme solution containing microsomes isolated from CHO cells overexpressing human 11beta -HSD1 (10-20 ug/ml of total protein) was added.
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 391.49, ALogP 5.66, HBA 2, HBD 0, PSA 29.54, QED 0.5
Compound (SMILES): C=C(C)CC1(c2ccccc2)CCN(C(C)(C)c2cn(-c3ccccc3)nn2)C(=O)O1
InChIKey: NGZAMCWHHYZIFK-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Scintillation Proximity Assay: The inhibition of a microsomal preparation of 11beta -HSD1 by compounds of the invention was measured essentially as previously described (K. Solly, S. S. Mundt, H. J. Zokian, G. J. Ding, A. Hermanowski-Vosatka, B. Strulovici, and W. Zheng, High-Throughput Screening of 11-Beta-Hydroxyseroid Dehydrogenase Type 1 in Scintillation Proximity Assay Format. Assay Drug Dev Technol 3 (2005) 377-384). All reactions were carried out at rt in 96 well clear flexible PET Microbeta plates (PerkinElmer). The assay begins by dispensing 49 ul of substrate solution (50 mM HEPES, pH 7.4, 100 mM KCl, 5 mM NaCl, 2 mM MgCl2, 2 mM NADPH and 160 nM [3H]cortisone (1 Ci/mmol)) and mixing in 1 uL of the test compounds in DMSO previously diluted in half-log increments (8 points) starting at 0.1 mM. After a 10 minute pre-incubation, 50 uL of enzyme solution containing microsomes isolated from CHO cells overexpressing human 11beta -HSD1 (10-20 ug/ml of total protein) was added.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 416.53, ALogP 5.21, HBA 5, HBD 0, PSA 60.25, QED 0.52