lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(Nc1cnccn1)N1CC(Oc2ccc(-c3ccccc3F)cn2)C1
InChIKey: MXZUCQMCGWGEFM-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition Assay: Human FAAH 1 activity was determined by measuring the liberation of the highly fluorescent 7-amino, 4-methyl Coumarin (AMC) generated during hydrolysis of the substrate arachidonoyl 7-amino, 4-methyl coumarin amide (AAMCA) by FAAH. Inhibition of human FAAH 1 activity was determined as a percentage reduction of the fluorescence determined in the absence of compound.The assay was carried out in black-walled, clear bottom, 384-well plates. 27.5 ul of human FAAH 1 protein (in FAAH assay buffer: 50 mM Hepes, 0.01% Triton X-100, 1 mM EDTA, 0.5 mg/ml BSA (fatty-acid-free), pH 8.2) was pre-incubated, at 10 nM, with increasing concentrations of compounds (2.5 ul in 100% DMSO) for 1 hour at room temperature. 2.5 ul of DMSO was added for total controls (100% FAAH activity) and 2.5 ul of URB-597, a known inhibitor of FAAH activity, (at a final, saturating, concentration of 10 uM) was used for non-specific controls (0 FAAH activity).
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 365.37, ALogP 2.97, HBA 5, HBD 1, PSA 80.24, QED 0.77
Compound (SMILES): COc1ccccc1-c1ccc(OC2CN(C(=O)Nc3cccnn3)C2)nc1
InChIKey: AIZRKFAOIQGVHS-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition Assay: Human FAAH 1 activity was determined by measuring the liberation of the highly fluorescent 7-amino, 4-methyl Coumarin (AMC) generated during hydrolysis of the substrate arachidonoyl 7-amino, 4-methyl coumarin amide (AAMCA) by FAAH. Inhibition of human FAAH 1 activity was determined as a percentage reduction of the fluorescence determined in the absence of compound.The assay was carried out in black-walled, clear bottom, 384-well plates. 27.5 ul of human FAAH 1 protein (in FAAH assay buffer: 50 mM Hepes, 0.01% Triton X-100, 1 mM EDTA, 0.5 mg/ml BSA (fatty-acid-free), pH 8.2) was pre-incubated, at 10 nM, with increasing concentrations of compounds (2.5 ul in 100% DMSO) for 1 hour at room temperature. 2.5 ul of DMSO was added for total controls (100% FAAH activity) and 2.5 ul of URB-597, a known inhibitor of FAAH activity, (at a final, saturating, concentration of 10 uM) was used for non-specific controls (0 FAAH activity).
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 377.4, ALogP 2.84, HBA 6, HBD 1, PSA 89.47, QED 0.74
Compound (SMILES): O=C(Nc1cccnn1)N1CC(Oc2ccc(-c3ccccc3F)cn2)C1
InChIKey: LIPUUWBEFCDHSI-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition Assay: Human FAAH 1 activity was determined by measuring the liberation of the highly fluorescent 7-amino, 4-methyl Coumarin (AMC) generated during hydrolysis of the substrate arachidonoyl 7-amino, 4-methyl coumarin amide (AAMCA) by FAAH. Inhibition of human FAAH 1 activity was determined as a percentage reduction of the fluorescence determined in the absence of compound.The assay was carried out in black-walled, clear bottom, 384-well plates. 27.5 ul of human FAAH 1 protein (in FAAH assay buffer: 50 mM Hepes, 0.01% Triton X-100, 1 mM EDTA, 0.5 mg/ml BSA (fatty-acid-free), pH 8.2) was pre-incubated, at 10 nM, with increasing concentrations of compounds (2.5 ul in 100% DMSO) for 1 hour at room temperature. 2.5 ul of DMSO was added for total controls (100% FAAH activity) and 2.5 ul of URB-597, a known inhibitor of FAAH activity, (at a final, saturating, concentration of 10 uM) was used for non-specific controls (0 FAAH activity).
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 365.37, ALogP 2.97, HBA 5, HBD 1, PSA 80.24, QED 0.77
Compound (SMILES): COC1C[C@H](OC(=O)c2cccnc2)C[C@@H](/C=C/c2c(-c3ccc(F)cc3)nc(N(C)S(C)(=O)=O)nc2C(C)C)O1
InChIKey: WBBZMHQYYBMWIC-OETWXICISA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 584.67, ALogP 4.59, HBA 9, HBD 0, PSA 120.81, QED 0.33
Compound (SMILES): CCCOC1C[C@H](OC(=O)c2cccnc2)C[C@@H](/C=C/c2c(-c3ccc(F)cc3)nc(N(C)S(C)(=O)=O)nc2C(C)C)O1
InChIKey: OFSINOWHTJMWNB-DQLLTYADSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 612.72, ALogP 5.37, HBA 9, HBD 0, PSA 120.81, QED 0.26
Compound (SMILES): CC(C)OC1C[C@H](OCc2ccccc2)C[C@@H](/C=C/c2c(-c3ccc(F)cc3)nc(N(C)S(C)(=O)=O)nc2C(C)C)O1
InChIKey: HPMKWIWLIPTFQV-FJAMEXCJSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 597.75, ALogP 6.33, HBA 7, HBD 0, PSA 90.85, QED 0.26
Compound (SMILES): CC(C)c1nc(N(C)S(C)(=O)=O)nc(-c2ccc(F)cc2)c1/C=C/[C@@H]1C[C@@H](OCc2ccccc2)CC(OC(C)(C)C)O1
InChIKey: COCIHEXJGZOSOJ-MXUUAITNSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P04035
Assay: Reductase Assay : The following procedure was followed using a HMG-CoA Reductase assay kit obtained from Sigma-Aldrich (catalogue number CS1090). The assay is based on the spectrophotometric measurement of the decrease in absorbance at 340 nm of NADPH in solution. A decrease in absorbance is caused by the oxidation of NADPH by the catalytic subunit of HMGR in the presence of the substrate HMG-CoA. Effective inhibition of the HMG-CoA leads to a reduction in oxidation of NADPH which in turn leads to a smaller reduction in the absorbance at 340 nm over time.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 611.78, ALogP 6.72, HBA 7, HBD 0, PSA 90.85, QED 0.25
Compound (SMILES): C=CCOC1C[C@H](OCc2ccccc2)C[C@@H](/C=C/c2c(-c3ccc(F)cc3)nc(N(C)S(C)(=O)=O)nc2C(C)C)O1
InChIKey: OMFUKTXBDFLJRM-FJAMEXCJSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P04035
Assay: Reductase Assay : The following procedure was followed using a HMG-CoA Reductase assay kit obtained from Sigma-Aldrich (catalogue number CS1090). The assay is based on the spectrophotometric measurement of the decrease in absorbance at 340 nm of NADPH in solution. A decrease in absorbance is caused by the oxidation of NADPH by the catalytic subunit of HMGR in the presence of the substrate HMG-CoA. Effective inhibition of the HMG-CoA leads to a reduction in oxidation of NADPH which in turn leads to a smaller reduction in the absorbance at 340 nm over time.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 595.74, ALogP 6.11, HBA 7, HBD 0, PSA 90.85, QED 0.23
Compound (SMILES): CC(C)c1nc(N(C)S(C)(=O)=O)nc(-c2ccc(F)cc2)c1/C=C/[C@@H]1C[C@@H](OCc2ccccc2)CC(OCC(Cl)(Cl)Cl)O1
InChIKey: HFUHFPLGHKFQPB-HQBUWMEKSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P04035
Assay: Reductase Assay : The following procedure was followed using a HMG-CoA Reductase assay kit obtained from Sigma-Aldrich (catalogue number CS1090). The assay is based on the spectrophotometric measurement of the decrease in absorbance at 340 nm of NADPH in solution. A decrease in absorbance is caused by the oxidation of NADPH by the catalytic subunit of HMGR in the presence of the substrate HMG-CoA. Effective inhibition of the HMG-CoA leads to a reduction in oxidation of NADPH which in turn leads to a smaller reduction in the absorbance at 340 nm over time.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 687.06, ALogP 7.29, HBA 7, HBD 0, PSA 90.85, QED 0.2
Compound (SMILES): CC(C)c1nc(N(C)S(C)(=O)=O)nc(-c2ccc(F)cc2)c1/C=C/[C@@H]1C[C@@H](O)CC(Oc2c(F)cc(F)cc2F)O1
InChIKey: MAPWRPSCIIWUDB-HHFGZVMTSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 595.62, ALogP 5.18, HBA 7, HBD 1, PSA 101.85, QED 0.36
Compound (SMILES): COc1ccc(OC2C[C@H](O)C[C@@H](/C=C/c3c(-c4ccc(F)cc4)nc(N(C)S(C)(=O)=O)nc3C(C)C)O2)c(OC)c1
InChIKey: CQYSSVVEFOVLEM-PCMIMOEYSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 601.7, ALogP 4.78, HBA 9, HBD 1, PSA 120.31, QED 0.35
Compound (SMILES): CC(C)c1nc(N(C)S(C)(=O)=O)nc(-c2ccc(F)cc2)c1/C=C/[C@@H]1C[C@@H](O)CC(OCC(Cl)(Cl)Cl)O1
InChIKey: XHZRVKRXKZCVLL-JKHXERJMSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 596.94, ALogP 5.07, HBA 7, HBD 1, PSA 101.85, QED 0.42
Compound (SMILES): CCCOC1C[C@H](O)C[C@@H](/C=C/c2c(-c3ccc(F)cc3)nc(N(C)S(C)(=O)=O)nc2C(C)C)O1
InChIKey: UCTBEFNFYMBJKW-KKZBYLJVSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 507.63, ALogP 4.11, HBA 7, HBD 1, PSA 101.85, QED 0.55
Compound (SMILES): COC1C[C@H](OC(=O)c2cccnc2)C[C@@H](CCn2c(-c3ccc(F)cc3)c(-c3ccccc3)c(C(=O)Nc3ccccc3)c2C(C)C)O1
InChIKey: ZFYLYTBCONNVCQ-DOTKWZJKSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 661.77, ALogP 8.5, HBA 7, HBD 1, PSA 91.68, QED 0.14
Compound (SMILES): CCCOC1C[C@H](O)C[C@@H](CCn2c(-c3ccc(F)cc3)c(-c3ccccc3)c(C(=O)Nc3ccccc3)c2C(C)C)O1
InChIKey: QSPZJDGFFMSQPC-KCUXUGRMSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 584.73, ALogP 8.02, HBA 5, HBD 2, PSA 72.72, QED 0.19
Compound (SMILES): CC(C)c1c(C(=O)Nc2ccccc2)c(-c2ccccc2)c(-c2ccc(F)cc2)n1CC[C@@H]1C[C@@H](O)CC(OC2CCCCC2)O1
InChIKey: YFXXPBMCYVXPEQ-FIDRQUTQSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 624.8, ALogP 8.94, HBA 5, HBD 2, PSA 72.72, QED 0.18
Compound (SMILES): CC(C)OC1C[C@H](OCc2ccccc2)C[C@@H](CCn2c(-c3ccc(F)cc3)c(-c3ccccc3)c(C(=O)Nc3ccccc3)c2C(C)C)O1
InChIKey: NWLKHHPNBMCPNS-QCUZFKLTSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 674.86, ALogP 10.24, HBA 5, HBD 1, PSA 61.72, QED 0.14
Compound (SMILES): CC(C)c1c(C(=O)Nc2ccccc2)c(-c2ccccc2)c(-c2ccc(F)cc2)n1CC[C@@H]1C[C@@H](OCc2ccccc2)CC(OC(C)(C)C)O1
InChIKey: IIVXJOHFZYFNLK-QCUZFKLTSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 688.88, ALogP 10.63, HBA 5, HBD 1, PSA 61.72, QED 0.14
Compound (SMILES): C=CCOC1C[C@H](OCc2ccccc2)C[C@@H](CCn2c(-c3ccc(F)cc3)c(-c3ccccc3)c(C(=O)Nc3ccccc3)c2C(C)C)O1
InChIKey: RFBDJMVSIWLFFC-QCUZFKLTSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 672.84, ALogP 10.02, HBA 5, HBD 1, PSA 61.72, QED 0.12
Compound (SMILES): COc1ccc(OC2C[C@H](O)C[C@@H](CCn3c(-c4ccc(F)cc4)c(-c4ccccc4)c(C(=O)Nc4ccccc4)c3C(C)C)O2)c(OC)c1
InChIKey: GOANSGMMXGHJHV-FOQVLGDDSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51639
Assay: Reductase Assay: All assays were carried out in a reaction buffer containing 100 nM KxPO4 at pH 7.2, 1 mM EDTA, 500 mM KCl and 1 mg/ml BSA. The concentrations of NADPH and HMG-CoA were both 200 μM. The enzyme concentration used is unknown although this concentration is 10-fold lower than that of the stock solution purchased. Inhibitors were dissolved in 75% DMSO. Where inhibitors were found to be insoluble or only partly soluble in 75% DMSO, 100% DMSO was used. Reactions were activated by the addition of enzyme and agitated for 12 seconds following the addition. Absorbance readings were then taken every 20 seconds for 600 seconds. In initial tests the concentration of each inhibitor was set at 50 nM to identify which compounds were the better inhibitors, compared to the known Pravastatin inhibitor.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 678.8, ALogP 8.69, HBA 7, HBD 2, PSA 91.18, QED 0.14
Compound (SMILES): COc1ccccc1NC(=O)C(=O)N/N=C(/CC(=O)c1cccs1)C(F)(F)F
InChIKey: DVEUPHCPHBSBAN-HMAPJEAMSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08592
Assay: Fluorescence (or FÃ¶rster) Resonance Energy Transfer (FRET) Assay: In this assay, assembly of Abeta 1-42 oligomer formation is monitored by FRET using N-terminal conjugates of fluorescein-Abeta 1-42 as both the donor and acceptor fluorophore (fluorescein-fluorescein Ro ~45 A). Abeta 1-42 monomers assembling into oligomeric species results in a decrease of fluorescence as the fluorescein labeled Abeta 1-42 peptides become proximal to each other and FRET efficiency increases. Inhibition of Abeta 1-42 assembly is observed as the absence or attenuation of fluorescein quenching.FRET and FP assays are performed in 384-well Corning Non-Binding Surface, black, opaque microtiter plates, and the assay buffer consists of 50 mM MOPS-Tris (pH 8.0) with 100 mM MgCl2. The assay volume, containing 0.2 uM FITC-Abeta (1-42) and 0.8 uM Abeta (1-42), is 50 ul and the temperature is 37 C. ADDL assembly is monitored on a Tecan GENios Pro plate reader, exciting at a wavelength of 485 nm and detecting emission at a wavelength of 515 nm.
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 413.38, ALogP 3, HBA 6, HBD 2, PSA 96.86, QED 0.33
Compound (SMILES): CCOC(=O)c1c(NC(=O)C(=O)N/N=C/c2cccc(OC)c2O)sc2c1CCC(C)C2
InChIKey: WQNLUIKFBJMWTA-FOKLQQMPSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08592
Assay: Fluorescence (or FÃ¶rster) Resonance Energy Transfer (FRET) Assay: In this assay, assembly of Abeta 1-42 oligomer formation is monitored by FRET using N-terminal conjugates of fluorescein-Abeta 1-42 as both the donor and acceptor fluorophore (fluorescein-fluorescein Ro ~45 A). Abeta 1-42 monomers assembling into oligomeric species results in a decrease of fluorescence as the fluorescein labeled Abeta 1-42 peptides become proximal to each other and FRET efficiency increases. Inhibition of Abeta 1-42 assembly is observed as the absence or attenuation of fluorescein quenching.FRET and FP assays are performed in 384-well Corning Non-Binding Surface, black, opaque microtiter plates, and the assay buffer consists of 50 mM MOPS-Tris (pH 8.0) with 100 mM MgCl2. The assay volume, containing 0.2 uM FITC-Abeta (1-42) and 0.8 uM Abeta (1-42), is 50 ul and the temperature is 37 C. ADDL assembly is monitored on a Tecan GENios Pro plate reader, exciting at a wavelength of 485 nm and detecting emission at a wavelength of 515 nm.
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 459.52, ALogP 2.85, HBA 8, HBD 3, PSA 126.32, QED 0.26
Compound (SMILES): CCOC(=O)c1c(NC(=O)C(=O)N/N=C/c2c(O)ccc3ccccc23)sc2c1CCC(C)C2
InChIKey: HTSXWHGXQOLKRU-LGJNPRDNSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08592
Assay: Fluorescence (or FÃ¶rster) Resonance Energy Transfer (FRET) Assay: In this assay, assembly of Abeta 1-42 oligomer formation is monitored by FRET using N-terminal conjugates of fluorescein-Abeta 1-42 as both the donor and acceptor fluorophore (fluorescein-fluorescein Ro ~45 A). Abeta 1-42 monomers assembling into oligomeric species results in a decrease of fluorescence as the fluorescein labeled Abeta 1-42 peptides become proximal to each other and FRET efficiency increases. Inhibition of Abeta 1-42 assembly is observed as the absence or attenuation of fluorescein quenching.FRET and FP assays are performed in 384-well Corning Non-Binding Surface, black, opaque microtiter plates, and the assay buffer consists of 50 mM MOPS-Tris (pH 8.0) with 100 mM MgCl2. The assay volume, containing 0.2 uM FITC-Abeta (1-42) and 0.8 uM Abeta (1-42), is 50 ul and the temperature is 37 C. ADDL assembly is monitored on a Tecan GENios Pro plate reader, exciting at a wavelength of 485 nm and detecting emission at a wavelength of 515 nm.
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 479.56, ALogP 4, HBA 7, HBD 3, PSA 117.09, QED 0.22
Compound (SMILES): CCOC(=O)c1c(NC(=O)C(=O)N/N=C/c2ccccc2O)sc2c1CCC(C)C2
InChIKey: AUKPPWBEXVSABK-SSDVNMTOSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08592
Assay: Fluorescence (or FÃ¶rster) Resonance Energy Transfer (FRET) Assay: In this assay, assembly of Abeta 1-42 oligomer formation is monitored by FRET using N-terminal conjugates of fluorescein-Abeta 1-42 as both the donor and acceptor fluorophore (fluorescein-fluorescein Ro ~45 A). Abeta 1-42 monomers assembling into oligomeric species results in a decrease of fluorescence as the fluorescein labeled Abeta 1-42 peptides become proximal to each other and FRET efficiency increases. Inhibition of Abeta 1-42 assembly is observed as the absence or attenuation of fluorescein quenching.FRET and FP assays are performed in 384-well Corning Non-Binding Surface, black, opaque microtiter plates, and the assay buffer consists of 50 mM MOPS-Tris (pH 8.0) with 100 mM MgCl2. The assay volume, containing 0.2 uM FITC-Abeta (1-42) and 0.8 uM Abeta (1-42), is 50 ul and the temperature is 37 C. ADDL assembly is monitored on a Tecan GENios Pro plate reader, exciting at a wavelength of 485 nm and detecting emission at a wavelength of 515 nm.
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 429.5, ALogP 2.84, HBA 7, HBD 3, PSA 117.09, QED 0.29
Compound (SMILES): COc1ccccc1NC(=O)C(=O)N1N=C(CC(C)C)CC1(O)C(F)(F)F
InChIKey: HYCRMNNPAJWJGN-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08592
Assay: Fluorescence (or FÃ¶rster) Resonance Energy Transfer (FRET) Assay: In this assay, assembly of Abeta 1-42 oligomer formation is monitored by FRET using N-terminal conjugates of fluorescein-Abeta 1-42 as both the donor and acceptor fluorophore (fluorescein-fluorescein Ro ~45 A). Abeta 1-42 monomers assembling into oligomeric species results in a decrease of fluorescence as the fluorescein labeled Abeta 1-42 peptides become proximal to each other and FRET efficiency increases. Inhibition of Abeta 1-42 assembly is observed as the absence or attenuation of fluorescein quenching.FRET and FP assays are performed in 384-well Corning Non-Binding Surface, black, opaque microtiter plates, and the assay buffer consists of 50 mM MOPS-Tris (pH 8.0) with 100 mM MgCl2. The assay volume, containing 0.2 uM FITC-Abeta (1-42) and 0.8 uM Abeta (1-42), is 50 ul and the temperature is 37 C. ADDL assembly is monitored on a Tecan GENios Pro plate reader, exciting at a wavelength of 485 nm and detecting emission at a wavelength of 515 nm.
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 387.36, ALogP 2.52, HBA 5, HBD 2, PSA 91.23, QED 0.78
Compound (SMILES): O=C(N/N=C/c1ccc2ccccc2c1O)c1ccccc1O
InChIKey: TUZKFRCVGZINHJ-YBFXNURJSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08592
Assay: Fluorescence (or FÃ¶rster) Resonance Energy Transfer (FRET) Assay: In this assay, assembly of Abeta 1-42 oligomer formation is monitored by FRET using N-terminal conjugates of fluorescein-Abeta 1-42 as both the donor and acceptor fluorophore (fluorescein-fluorescein Ro ~45 A). Abeta 1-42 monomers assembling into oligomeric species results in a decrease of fluorescence as the fluorescein labeled Abeta 1-42 peptides become proximal to each other and FRET efficiency increases. Inhibition of Abeta 1-42 assembly is observed as the absence or attenuation of fluorescein quenching.FRET and FP assays are performed in 384-well Corning Non-Binding Surface, black, opaque microtiter plates, and the assay buffer consists of 50 mM MOPS-Tris (pH 8.0) with 100 mM MgCl2. The assay volume, containing 0.2 uM FITC-Abeta (1-42) and 0.8 uM Abeta (1-42), is 50 ul and the temperature is 37 C. ADDL assembly is monitored on a Tecan GENios Pro plate reader, exciting at a wavelength of 485 nm and detecting emission at a wavelength of 515 nm.
Measurement: IC50 = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 306.32, ALogP 3.01, HBA 4, HBD 3, PSA 81.92, QED 0.51
Compound (SMILES): O=C(O)c1cccc2[nH]c(-c3ccc(OCc4ccccc4)cc3)nc12
InChIKey: YNLOUCFKPZTKOY-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 4950 nM (pChEMBL 5.300000190734863)
Descriptors: MW 344.37, ALogP 4.51, HBA 3, HBD 2, PSA 75.21, QED 0.56
Compound (SMILES): COc1cccc(-c2ccc(-c3nc4c(C(=O)O)cccc4[nH]3)c(F)c2)c1
InChIKey: XEQJVYACUJGESM-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 616 nM (pChEMBL 6.210000038146973)
Descriptors: MW 362.36, ALogP 4.74, HBA 3, HBD 2, PSA 75.21, QED 0.55
Compound (SMILES): O=C(O)c1cc(Br)cc2[nH]c(-c3ccc(-c4ccccc4)cc3)nc12
InChIKey: ZHCOASRCBFJYAQ-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 574 nM (pChEMBL 6.239999771118164)
Descriptors: MW 393.24, ALogP 5.36, HBA 2, HBD 2, PSA 65.98, QED 0.49
Compound (SMILES): Cn1c(-c2ccc(-c3ccccc3)cc2)nc2cccc(C(=O)O)c21
InChIKey: RRVVLIAKAIQDJN-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 328.37, ALogP 4.61, HBA 3, HBD 1, PSA 55.12, QED 0.6
Compound (SMILES): O=C(O)c1cccc2[nH]c(-c3cccc(Oc4ccccc4)c3)nc12
InChIKey: VLXGJZOPSSMBQU-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 330.34, ALogP 4.72, HBA 3, HBD 2, PSA 75.21, QED 0.57
Compound (SMILES): O=C(O)c1cccc2[nH]c(-c3ccc(Oc4ccccc4)cc3)nc12
InChIKey: PBAUELOAXPSLHU-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 2870 nM (pChEMBL 5.539999961853027)
Descriptors: MW 330.34, ALogP 4.72, HBA 3, HBD 2, PSA 75.21, QED 0.57
Compound (SMILES): Cc1cc(C(=O)O)c2nc(-c3ccc(-c4ccccc4)cc3)[nH]c2c1
InChIKey: XKLFYTKDXSVKQI-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 304 nM (pChEMBL 6.519999980926514)
Descriptors: MW 328.37, ALogP 4.9, HBA 2, HBD 2, PSA 65.98, QED 0.56
Compound (SMILES): O=C(O)c1cccc2[nH]c(-c3ccc(-c4ccccc4F)cc3)nc12
InChIKey: TTZPIVMCIXWFFX-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 332.33, ALogP 4.73, HBA 2, HBD 2, PSA 65.98, QED 0.57
Compound (SMILES): O=C(O)c1cccc2[nH]c(-c3ccc(-c4cccc(F)c4)cc3)nc12
InChIKey: XMYCDPCIKQYCFI-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 3790 nM (pChEMBL 5.420000076293945)
Descriptors: MW 332.33, ALogP 4.73, HBA 2, HBD 2, PSA 65.98, QED 0.57
Compound (SMILES): O=C(O)c1cccc2[nH]c(-c3ccc(-c4cccc(OC(F)(F)F)c4)cc3)nc12
InChIKey: IPPQYUWLGMIHKW-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 398.34, ALogP 5.49, HBA 3, HBD 2, PSA 75.21, QED 0.48
Compound (SMILES): O=C(O)c1cccc2nc(-c3ccc(-c4ccccc4)cc3)oc12
InChIKey: HLZCFJDKMCVQFA-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 3030 nM (pChEMBL 5.519999980926514)
Descriptors: MW 315.33, ALogP 4.86, HBA 3, HBD 1, PSA 63.33, QED 0.59
Compound (SMILES): COc1cc(-c2nc3c(C(=O)O)cccc3[nH]2)cc(OC)c1-c1ccccc1
InChIKey: UJCNESUGJLTDHA-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 975 nM (pChEMBL 6.010000228881836)
Descriptors: MW 374.4, ALogP 4.61, HBA 4, HBD 2, PSA 84.44, QED 0.53
Compound (SMILES): O=C(O)c1cccc2[nH]c(-c3c(F)c(F)c(-c4ccccc4)c(F)c3F)nc12
InChIKey: IKHBMNRPSPINLM-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzyme Assay: The DHODH activity assay is a coupled enzyme assay in which oxidation of DHO and subsequent reduction of ubiquinone are stoichiometrically equivalent to the reduction of DCIP (2,6-dichlorophenol). The reduction of DCIP is accompanied by a loss of absorbance at 610 nm.Reagents Used:L-Dihydroorotic acid, Sigma, D7128, 2,6-Dichloroindophenol sodium salt hydrate, sigma, D1878 Dimethyl sulfoxide (DMSO), spectroscopic grade purchased from Spectrochem, cat no. 0704209, B. no.--3183650 Decylubiquinone, Sigma, D7911Preparation of Solutions/Reagents:Buffer Preparation: 50 mM tris HCl, 150 mM KCl, and pH 8.0, 0.8% triton.L-Dihydroorotic acid stock solution of 20 mM in buffer2,6-Dichloroindophenol Sodium salt hydrate stock solution of 20 mM in bufferDecylubiquinone stock solution of 20 mM in bufferDMSO used as vehicleProcedure:5 .mu.L of Dimethyl sulfoxide or a compound of formula I in DMSO solution was added to the wells of a 96 well plate. Compounds of formula I were measured at 10 .mu.M.
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 386.3, ALogP 5.15, HBA 2, HBD 2, PSA 65.98, QED 0.38