lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCC(N(C)C)C2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: PANUCCHSDROJBK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 533.68, ALogP 5.47, HBA 7, HBD 2, PSA 86.28, QED 0.33
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CC[C@@H](N(C)C)C2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: PANUCCHSDROJBK-FIQOPJFZSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 533.68, ALogP 5.47, HBA 7, HBD 2, PSA 86.28, QED 0.33
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CC[C@@H]3N2CCN(C)CC2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: YTHUQGIGAIZNIM-LJAQVGFWSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 519.65, ALogP 5.08, HBA 7, HBD 2, PSA 86.28, QED 0.37
Compound (SMILES): Cc1ccc(NC(=O)c2ccc3c(c2)CCC3N2CCN(C)CC2)cc1Nc1nccc(-c2ccncc2)n1
InChIKey: GMYQHOQOEQWZGN-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Enzyme Assay: The activity of the compounds of this invention on Abl, c-Kit and PDGFR kinases was tested by Mobility Shift Assay (MSA). Kinase buffer: 62.5 mM HEPES, pH 7.5; 0.001875% Brij-35; 12.5 mM MgCl2; 2.5 mM DTT. Stop buffer: 100 mM HEPES, pH 7.5; 0.015% Brij-35; 0.2% coating agent 3; 50 mM EDTA. Preparation of kinase solution: Kinase solution was obtained by dissolving kinases in the kinase buffer mentioned above. With regard to c-Kit kinase, the pre-activation treatments should be carried out as follows. 700 nM c-Kit, 2 mM ATP, 4 mM DTT and 10 mM MgCl2 were dissolved in kinase buffer. After being incubated at 28° C. for 15 minutes, the solution was added to the kinase buffer.
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 519.65, ALogP 5.08, HBA 7, HBD 2, PSA 86.28, QED 0.37
Compound (SMILES): COCCOc1cnc(C(=O)Nc2cccc(C3(C)CC(=O)N(C)C(N)=N3)c2)cn1
InChIKey: NAJNDLWHMNSIOI-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibitory Assay: First, 48.5 μl portions of a solution of substrate peptide (Biotin-XSEVNLDAEFRHDSGC-Eu: X=ε-amino-n-capronic acid, Eu=Europium cryptate) were put into respective wells of a 96-well half area microplate (black microplate, Costar). Then, 0.5 μl of a test compound (DMSO (dimethyl sulfoxide) solution) and 1 μl of Recombinant human BACE-1 (R&D systems) were added to each of the wells, and they were reacted for 3 hours at 30° C. The substrate peptide was synthesized by reacting Biotin-XSEVNLDAEFRHDSGC (PEPTIDE INSTITUTE, INC.) with Cryptate TBPCOOH mono SMP (CIS bio international). The final concentration of the substrate peptide was set to 18 nM, and the final concentration of Recombinant human BACE-1 was set to 7.4 nM. The reaction buffer used was a sodium acetate buffer (50 mM sodium acetate, pH 5.0, 0.008% Triton X-100).
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 412.45, ALogP 1.15, HBA 8, HBD 2, PSA 132.03, QED 0.65
Compound (SMILES): C#CCOc1cnc(C(=O)Nc2cccc(C3(C)CC(=O)N(C)C(N)=N3)c2)cn1
InChIKey: BZORNRLJYSMPOP-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibitory Assay: First, 48.5 μl portions of a solution of substrate peptide (Biotin-XSEVNLDAEFRHDSGC-Eu: X=ε-amino-n-capronic acid, Eu=Europium cryptate) were put into respective wells of a 96-well half area microplate (black microplate, Costar). Then, 0.5 μl of a test compound (DMSO (dimethyl sulfoxide) solution) and 1 μl of Recombinant human BACE-1 (R&D systems) were added to each of the wells, and they were reacted for 3 hours at 30° C. The substrate peptide was synthesized by reacting Biotin-XSEVNLDAEFRHDSGC (PEPTIDE INSTITUTE, INC.) with Cryptate TBPCOOH mono SMP (CIS bio international). The final concentration of the substrate peptide was set to 18 nM, and the final concentration of Recombinant human BACE-1 was set to 7.4 nM. The reaction buffer used was a sodium acetate buffer (50 mM sodium acetate, pH 5.0, 0.008% Triton X-100).
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 392.42, ALogP 1.13, HBA 7, HBD 2, PSA 122.8, QED 0.74
Compound (SMILES): CC#CCOc1cnc(C(=O)Nc2cccc(C3(C)CC(=O)N(C)C(N)=N3)c2)cn1
InChIKey: RAZCVUGUPNQOCM-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibitory Assay: First, 48.5 μl portions of a solution of substrate peptide (Biotin-XSEVNLDAEFRHDSGC-Eu: X=ε-amino-n-capronic acid, Eu=Europium cryptate) were put into respective wells of a 96-well half area microplate (black microplate, Costar). Then, 0.5 μl of a test compound (DMSO (dimethyl sulfoxide) solution) and 1 μl of Recombinant human BACE-1 (R&D systems) were added to each of the wells, and they were reacted for 3 hours at 30° C. The substrate peptide was synthesized by reacting Biotin-XSEVNLDAEFRHDSGC (PEPTIDE INSTITUTE, INC.) with Cryptate TBPCOOH mono SMP (CIS bio international). The final concentration of the substrate peptide was set to 18 nM, and the final concentration of Recombinant human BACE-1 was set to 7.4 nM. The reaction buffer used was a sodium acetate buffer (50 mM sodium acetate, pH 5.0, 0.008% Triton X-100).
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 406.45, ALogP 1.52, HBA 7, HBD 2, PSA 122.8, QED 0.73
Compound (SMILES): CN1C(=O)CC(C)(c2cccc(NC(=O)c3cnc(Cl)cn3)c2)N=C1N
InChIKey: WHPXSUXTRBXIHO-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibitory Assay: First, 48.5 μl portions of a solution of substrate peptide (Biotin-XSEVNLDAEFRHDSGC-Eu: X=ε-amino-n-capronic acid, Eu=Europium cryptate) were put into respective wells of a 96-well half area microplate (black microplate, Costar). Then, 0.5 μl of a test compound (DMSO (dimethyl sulfoxide) solution) and 1 μl of Recombinant human BACE-1 (R&D systems) were added to each of the wells, and they were reacted for 3 hours at 30° C. The substrate peptide was synthesized by reacting Biotin-XSEVNLDAEFRHDSGC (PEPTIDE INSTITUTE, INC.) with Cryptate TBPCOOH mono SMP (CIS bio international). The final concentration of the substrate peptide was set to 18 nM, and the final concentration of Recombinant human BACE-1 was set to 7.4 nM. The reaction buffer used was a sodium acetate buffer (50 mM sodium acetate, pH 5.0, 0.008% Triton X-100).
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 372.82, ALogP 1.77, HBA 6, HBD 2, PSA 113.57, QED 0.85
Compound (SMILES): COc1cnc(C(=O)Nc2cccc(C3(C)CC(=O)N(C)C(N)=N3)c2)cn1
InChIKey: BLFCZMABWGILKE-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibitory Assay: First, 48.5 μl portions of a solution of substrate peptide (Biotin-XSEVNLDAEFRHDSGC-Eu: X=ε-amino-n-capronic acid, Eu=Europium cryptate) were put into respective wells of a 96-well half area microplate (black microplate, Costar). Then, 0.5 μl of a test compound (DMSO (dimethyl sulfoxide) solution) and 1 μl of Recombinant human BACE-1 (R&D systems) were added to each of the wells, and they were reacted for 3 hours at 30° C. The substrate peptide was synthesized by reacting Biotin-XSEVNLDAEFRHDSGC (PEPTIDE INSTITUTE, INC.) with Cryptate TBPCOOH mono SMP (CIS bio international). The final concentration of the substrate peptide was set to 18 nM, and the final concentration of Recombinant human BACE-1 was set to 7.4 nM. The reaction buffer used was a sodium acetate buffer (50 mM sodium acetate, pH 5.0, 0.008% Triton X-100).
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 368.4, ALogP 1.13, HBA 7, HBD 2, PSA 122.8, QED 0.83
Compound (SMILES): COc1cnc(C(=O)Nc2cccc(CNc3cccnc3N)c2)cn1
InChIKey: VOGMQIUOXSCWIG-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibitory Assay: First, 48.5 μl portions of a solution of substrate peptide (Biotin-XSEVNLDAEFRHDSGC-Eu: X=ε-amino-n-capronic acid, Eu=Europium cryptate) were put into respective wells of a 96-well half area microplate (black microplate, Costar). Then, 0.5 μl of a test compound (DMSO (dimethyl sulfoxide) solution) and 1 μl of Recombinant human BACE-1 (R&D systems) were added to each of the wells, and they were reacted for 3 hours at 30° C. The substrate peptide was synthesized by reacting Biotin-XSEVNLDAEFRHDSGC (PEPTIDE INSTITUTE, INC.) with Cryptate TBPCOOH mono SMP (CIS bio international). The final concentration of the substrate peptide was set to 18 nM, and the final concentration of Recombinant human BACE-1 was set to 7.4 nM. The reaction buffer used was a sodium acetate buffer (50 mM sodium acetate, pH 5.0, 0.008% Triton X-100).
Measurement: IC50 = 1985 nM (pChEMBL 5.699999809265137)
Descriptors: MW 350.38, ALogP 2.33, HBA 7, HBD 3, PSA 115.05, QED 0.62
Compound (SMILES): COCCOc1cnc(C(=O)Nc2cccc(CNc3cccnc3N)c2)cn1
InChIKey: GXWIPFVJHSXRGD-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibitory Assay: First, 48.5 μl portions of a solution of substrate peptide (Biotin-XSEVNLDAEFRHDSGC-Eu: X=ε-amino-n-capronic acid, Eu=Europium cryptate) were put into respective wells of a 96-well half area microplate (black microplate, Costar). Then, 0.5 μl of a test compound (DMSO (dimethyl sulfoxide) solution) and 1 μl of Recombinant human BACE-1 (R&D systems) were added to each of the wells, and they were reacted for 3 hours at 30° C. The substrate peptide was synthesized by reacting Biotin-XSEVNLDAEFRHDSGC (PEPTIDE INSTITUTE, INC.) with Cryptate TBPCOOH mono SMP (CIS bio international). The final concentration of the substrate peptide was set to 18 nM, and the final concentration of Recombinant human BACE-1 was set to 7.4 nM. The reaction buffer used was a sodium acetate buffer (50 mM sodium acetate, pH 5.0, 0.008% Triton X-100).
Measurement: IC50 = 3176 nM (pChEMBL 5.5)
Descriptors: MW 394.44, ALogP 2.34, HBA 8, HBD 3, PSA 124.28, QED 0.47
Compound (SMILES): C#CCOc1cnc(C(=O)Nc2cccc(CNc3cccnc3N)c2)cn1
InChIKey: GDAPCOAWIWVVSW-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibitory Assay: First, 48.5 μl portions of a solution of substrate peptide (Biotin-XSEVNLDAEFRHDSGC-Eu: X=ε-amino-n-capronic acid, Eu=Europium cryptate) were put into respective wells of a 96-well half area microplate (black microplate, Costar). Then, 0.5 μl of a test compound (DMSO (dimethyl sulfoxide) solution) and 1 μl of Recombinant human BACE-1 (R&D systems) were added to each of the wells, and they were reacted for 3 hours at 30° C. The substrate peptide was synthesized by reacting Biotin-XSEVNLDAEFRHDSGC (PEPTIDE INSTITUTE, INC.) with Cryptate TBPCOOH mono SMP (CIS bio international). The final concentration of the substrate peptide was set to 18 nM, and the final concentration of Recombinant human BACE-1 was set to 7.4 nM. The reaction buffer used was a sodium acetate buffer (50 mM sodium acetate, pH 5.0, 0.008% Triton X-100).
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 374.4, ALogP 2.33, HBA 7, HBD 3, PSA 115.05, QED 0.54
Compound (SMILES): CC#CCOc1cnc(C(=O)Nc2cccc(CNc3cccnc3N)c2)cn1
InChIKey: YSWDNAPAEVGGIX-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibitory Assay: First, 48.5 μl portions of a solution of substrate peptide (Biotin-XSEVNLDAEFRHDSGC-Eu: X=ε-amino-n-capronic acid, Eu=Europium cryptate) were put into respective wells of a 96-well half area microplate (black microplate, Costar). Then, 0.5 μl of a test compound (DMSO (dimethyl sulfoxide) solution) and 1 μl of Recombinant human BACE-1 (R&D systems) were added to each of the wells, and they were reacted for 3 hours at 30° C. The substrate peptide was synthesized by reacting Biotin-XSEVNLDAEFRHDSGC (PEPTIDE INSTITUTE, INC.) with Cryptate TBPCOOH mono SMP (CIS bio international). The final concentration of the substrate peptide was set to 18 nM, and the final concentration of Recombinant human BACE-1 was set to 7.4 nM. The reaction buffer used was a sodium acetate buffer (50 mM sodium acetate, pH 5.0, 0.008% Triton X-100).
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 388.43, ALogP 2.72, HBA 7, HBD 3, PSA 115.05, QED 0.53
Compound (SMILES): O=C1CCCN1C[C@]1(O)CC[C@]2(CCN(c3ccc(C(F)(F)F)cc3)C2=O)CC1
InChIKey: MPXIIZXHGWWBCR-BGYRXZFFSA-N
Target: Hormone-sensitive lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q05469
Assay: Enzyme Inhibition Assay: HSL enzyme activity was measured by a colorimetric assay using 2,3-dimercapto-1-propanol tributyrate (Aldrich, St. Louis, Mo.) as a substrate. Typically, 1.5 mM 2,3-dimercapto-1-propanol tributyrate (DMPT) in 100 mM MOPS, pH 7.2, 0.2 mg/ml fatty acid-free BSA was prepared by sonication at 4° C. to homogenous suspension. Test compounds (2 mM stock in DMSO) were diluted 3 fold in series in DMSO. Compound solutions were diluted 24 fold in 1.5 mM DMPT containing solution and 18 ul per well was added to 384-well microplates (Corning Costar). Twelve microliters per well of human HSL (15 ug/ml) was added and the reaction mixture was incubated at 37° C. for 20 minutes. Six microliters of 12 mM dithio-bis-(2-nitrobenzoic acid) (DTNB) in DMSO plus 1.2% SDS and 0.6% Triton X-100 were added and the mixture was incubated at room temperature for 15 minutes.
Measurement: IC50 = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 410.44, ALogP 3.36, HBA 3, HBD 1, PSA 60.85, QED 0.83
Compound (SMILES): O=C1CCCCN1C[C@]1(O)CC[C@]2(CCN(c3ccc(C(F)(F)F)cc3)C2=O)CC1
InChIKey: REOQTRMOISIUKA-OYRHEFFESA-N
Target: Hormone-sensitive lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q05469
Assay: Enzyme Inhibition Assay: HSL enzyme activity was measured by a colorimetric assay using 2,3-dimercapto-1-propanol tributyrate (Aldrich, St. Louis, Mo.) as a substrate. Typically, 1.5 mM 2,3-dimercapto-1-propanol tributyrate (DMPT) in 100 mM MOPS, pH 7.2, 0.2 mg/ml fatty acid-free BSA was prepared by sonication at 4° C. to homogenous suspension. Test compounds (2 mM stock in DMSO) were diluted 3 fold in series in DMSO. Compound solutions were diluted 24 fold in 1.5 mM DMPT containing solution and 18 ul per well was added to 384-well microplates (Corning Costar). Twelve microliters per well of human HSL (15 ug/ml) was added and the reaction mixture was incubated at 37° C. for 20 minutes. Six microliters of 12 mM dithio-bis-(2-nitrobenzoic acid) (DTNB) in DMSO plus 1.2% SDS and 0.6% Triton X-100 were added and the mixture was incubated at room temperature for 15 minutes.
Measurement: IC50 = 68.1 nM (pChEMBL 7.170000076293945)
Descriptors: MW 424.46, ALogP 3.75, HBA 3, HBD 1, PSA 60.85, QED 0.8
Compound (SMILES): CC(C)Oc1ccc(N2CC[C@]3(CC[C@@](O)(CN4CCCC4=O)CC3)C2=O)cc1
InChIKey: ZWOWLGMHKOBGRV-ZRZAMGCNSA-N
Target: Hormone-sensitive lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q05469
Assay: Enzyme Inhibition Assay: HSL enzyme activity was measured by a colorimetric assay using 2,3-dimercapto-1-propanol tributyrate (Aldrich, St. Louis, Mo.) as a substrate. Typically, 1.5 mM 2,3-dimercapto-1-propanol tributyrate (DMPT) in 100 mM MOPS, pH 7.2, 0.2 mg/ml fatty acid-free BSA was prepared by sonication at 4° C. to homogenous suspension. Test compounds (2 mM stock in DMSO) were diluted 3 fold in series in DMSO. Compound solutions were diluted 24 fold in 1.5 mM DMPT containing solution and 18 ul per well was added to 384-well microplates (Corning Costar). Twelve microliters per well of human HSL (15 ug/ml) was added and the reaction mixture was incubated at 37° C. for 20 minutes. Six microliters of 12 mM dithio-bis-(2-nitrobenzoic acid) (DTNB) in DMSO plus 1.2% SDS and 0.6% Triton X-100 were added and the mixture was incubated at room temperature for 15 minutes.
Measurement: IC50 = 50.9 nM (pChEMBL 7.289999961853027)
Descriptors: MW 400.52, ALogP 3.12, HBA 4, HBD 1, PSA 70.08, QED 0.82
Compound (SMILES): CC(C)Oc1ccc(N2CC[C@]3(CC[C@@](O)(CN4CCCCC4=O)CC3)C2=O)cc1
InChIKey: MZTCLPDWZWEGMR-PSWAGMNNSA-N
Target: Hormone-sensitive lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q05469
Assay: Enzyme Inhibition Assay: HSL enzyme activity was measured by a colorimetric assay using 2,3-dimercapto-1-propanol tributyrate (Aldrich, St. Louis, Mo.) as a substrate. Typically, 1.5 mM 2,3-dimercapto-1-propanol tributyrate (DMPT) in 100 mM MOPS, pH 7.2, 0.2 mg/ml fatty acid-free BSA was prepared by sonication at 4° C. to homogenous suspension. Test compounds (2 mM stock in DMSO) were diluted 3 fold in series in DMSO. Compound solutions were diluted 24 fold in 1.5 mM DMPT containing solution and 18 ul per well was added to 384-well microplates (Corning Costar). Twelve microliters per well of human HSL (15 ug/ml) was added and the reaction mixture was incubated at 37° C. for 20 minutes. Six microliters of 12 mM dithio-bis-(2-nitrobenzoic acid) (DTNB) in DMSO plus 1.2% SDS and 0.6% Triton X-100 were added and the mixture was incubated at room temperature for 15 minutes.
Measurement: IC50 = 27.4 nM (pChEMBL 7.559999942779541)
Descriptors: MW 414.55, ALogP 3.51, HBA 4, HBD 1, PSA 70.08, QED 0.8
Compound (SMILES): CC(C)Oc1ccc(N2CC[C@]3(CC[C@@](O)(COCC(F)F)CC3)C2=O)cc1
InChIKey: XMGFBIJRNSFBMV-OYRHEFFESA-N
Target: Hormone-sensitive lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q05469
Assay: Enzyme Inhibition Assay: HSL enzyme activity was measured by a colorimetric assay using 2,3-dimercapto-1-propanol tributyrate (Aldrich, St. Louis, Mo.) as a substrate. Typically, 1.5 mM 2,3-dimercapto-1-propanol tributyrate (DMPT) in 100 mM MOPS, pH 7.2, 0.2 mg/ml fatty acid-free BSA was prepared by sonication at 4° C. to homogenous suspension. Test compounds (2 mM stock in DMSO) were diluted 3 fold in series in DMSO. Compound solutions were diluted 24 fold in 1.5 mM DMPT containing solution and 18 ul per well was added to 384-well microplates (Corning Costar). Twelve microliters per well of human HSL (15 ug/ml) was added and the reaction mixture was incubated at 37° C. for 20 minutes. Six microliters of 12 mM dithio-bis-(2-nitrobenzoic acid) (DTNB) in DMSO plus 1.2% SDS and 0.6% Triton X-100 were added and the mixture was incubated at room temperature for 15 minutes.
Measurement: IC50 = 16.3 nM (pChEMBL 7.789999961853027)
Descriptors: MW 397.46, ALogP 3.78, HBA 4, HBD 1, PSA 59, QED 0.76
Compound (SMILES): CC(C)Oc1ccc(N2CC[C@]3(CC[C@@](O)(CN4CCCC4=O)CC3)C2=O)cn1
InChIKey: CBTYMQZEPLCLEK-SZPZYZBQSA-N
Target: Hormone-sensitive lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q05469
Assay: Enzyme Inhibition Assay: HSL enzyme activity was measured by a colorimetric assay using 2,3-dimercapto-1-propanol tributyrate (Aldrich, St. Louis, Mo.) as a substrate. Typically, 1.5 mM 2,3-dimercapto-1-propanol tributyrate (DMPT) in 100 mM MOPS, pH 7.2, 0.2 mg/ml fatty acid-free BSA was prepared by sonication at 4° C. to homogenous suspension. Test compounds (2 mM stock in DMSO) were diluted 3 fold in series in DMSO. Compound solutions were diluted 24 fold in 1.5 mM DMPT containing solution and 18 ul per well was added to 384-well microplates (Corning Costar). Twelve microliters per well of human HSL (15 ug/ml) was added and the reaction mixture was incubated at 37° C. for 20 minutes. Six microliters of 12 mM dithio-bis-(2-nitrobenzoic acid) (DTNB) in DMSO plus 1.2% SDS and 0.6% Triton X-100 were added and the mixture was incubated at room temperature for 15 minutes.
Measurement: IC50 = 264 nM (pChEMBL 6.579999923706055)
Descriptors: MW 401.51, ALogP 2.52, HBA 5, HBD 1, PSA 82.97, QED 0.82
Compound (SMILES): CC(C)Oc1ccc(N2CC[C@]3(CC[C@@](O)(COCC(F)(F)F)CC3)C2=O)cn1
InChIKey: RRDLYIRHUKUQGX-KDURUIRLSA-N
Target: Hormone-sensitive lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q05469
Assay: Enzyme Inhibition Assay: HSL enzyme activity was measured by a colorimetric assay using 2,3-dimercapto-1-propanol tributyrate (Aldrich, St. Louis, Mo.) as a substrate. Typically, 1.5 mM 2,3-dimercapto-1-propanol tributyrate (DMPT) in 100 mM MOPS, pH 7.2, 0.2 mg/ml fatty acid-free BSA was prepared by sonication at 4° C. to homogenous suspension. Test compounds (2 mM stock in DMSO) were diluted 3 fold in series in DMSO. Compound solutions were diluted 24 fold in 1.5 mM DMPT containing solution and 18 ul per well was added to 384-well microplates (Corning Costar). Twelve microliters per well of human HSL (15 ug/ml) was added and the reaction mixture was incubated at 37° C. for 20 minutes. Six microliters of 12 mM dithio-bis-(2-nitrobenzoic acid) (DTNB) in DMSO plus 1.2% SDS and 0.6% Triton X-100 were added and the mixture was incubated at room temperature for 15 minutes.
Measurement: IC50 = 13.7 nM (pChEMBL 7.860000133514404)
Descriptors: MW 416.44, ALogP 3.48, HBA 5, HBD 1, PSA 71.89, QED 0.77
Compound (SMILES): O=C1CCCN1C[C@]1(O)CC[C@]2(CCN(c3ccc([C@@H](O)C(F)(F)F)cc3)C2=O)CC1
InChIKey: YKJJSIOUGHZZCZ-NRSPTQNISA-N
Target: Hormone-sensitive lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q05469
Assay: Enzyme Inhibition Assay: HSL enzyme activity was measured by a colorimetric assay using 2,3-dimercapto-1-propanol tributyrate (Aldrich, St. Louis, Mo.) as a substrate. Typically, 1.5 mM 2,3-dimercapto-1-propanol tributyrate (DMPT) in 100 mM MOPS, pH 7.2, 0.2 mg/ml fatty acid-free BSA was prepared by sonication at 4° C. to homogenous suspension. Test compounds (2 mM stock in DMSO) were diluted 3 fold in series in DMSO. Compound solutions were diluted 24 fold in 1.5 mM DMPT containing solution and 18 ul per well was added to 384-well microplates (Corning Costar). Twelve microliters per well of human HSL (15 ug/ml) was added and the reaction mixture was incubated at 37° C. for 20 minutes. Six microliters of 12 mM dithio-bis-(2-nitrobenzoic acid) (DTNB) in DMSO plus 1.2% SDS and 0.6% Triton X-100 were added and the mixture was incubated at room temperature for 15 minutes.
Measurement: IC50 = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 440.46, ALogP 2.93, HBA 4, HBD 2, PSA 81.08, QED 0.75
Compound (SMILES): C[C@H](Oc1ccc(N2CC[C@]3(CC[C@@](O)(CN4CCCC4=O)CC3)C2=O)cn1)C(F)(F)F
InChIKey: BZVIQGOMSOMKSC-ONGXBYRLSA-N
Target: Hormone-sensitive lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q05469
Assay: Enzyme Inhibition Assay: HSL enzyme activity was measured by a colorimetric assay using 2,3-dimercapto-1-propanol tributyrate (Aldrich, St. Louis, Mo.) as a substrate. Typically, 1.5 mM 2,3-dimercapto-1-propanol tributyrate (DMPT) in 100 mM MOPS, pH 7.2, 0.2 mg/ml fatty acid-free BSA was prepared by sonication at 4° C. to homogenous suspension. Test compounds (2 mM stock in DMSO) were diluted 3 fold in series in DMSO. Compound solutions were diluted 24 fold in 1.5 mM DMPT containing solution and 18 ul per well was added to 384-well microplates (Corning Costar). Twelve microliters per well of human HSL (15 ug/ml) was added and the reaction mixture was incubated at 37° C. for 20 minutes. Six microliters of 12 mM dithio-bis-(2-nitrobenzoic acid) (DTNB) in DMSO plus 1.2% SDS and 0.6% Triton X-100 were added and the mixture was incubated at room temperature for 15 minutes.
Measurement: IC50 = 41.8 nM (pChEMBL 7.380000114440918)
Descriptors: MW 455.48, ALogP 3.06, HBA 5, HBD 1, PSA 82.97, QED 0.74
Compound (SMILES): C[C@H](Oc1ccc(N2CC[C@]3(CC[C@@](O)(COCCF)CC3)C2=O)cn1)C(F)(F)F
InChIKey: KJGFPRVHPPISPG-ZOCIIQOWSA-N
Target: Hormone-sensitive lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q05469
Assay: Enzyme Inhibition Assay: HSL enzyme activity was measured by a colorimetric assay using 2,3-dimercapto-1-propanol tributyrate (Aldrich, St. Louis, Mo.) as a substrate. Typically, 1.5 mM 2,3-dimercapto-1-propanol tributyrate (DMPT) in 100 mM MOPS, pH 7.2, 0.2 mg/ml fatty acid-free BSA was prepared by sonication at 4° C. to homogenous suspension. Test compounds (2 mM stock in DMSO) were diluted 3 fold in series in DMSO. Compound solutions were diluted 24 fold in 1.5 mM DMPT containing solution and 18 ul per well was added to 384-well microplates (Corning Costar). Twelve microliters per well of human HSL (15 ug/ml) was added and the reaction mixture was incubated at 37° C. for 20 minutes. Six microliters of 12 mM dithio-bis-(2-nitrobenzoic acid) (DTNB) in DMSO plus 1.2% SDS and 0.6% Triton X-100 were added and the mixture was incubated at room temperature for 15 minutes.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 434.43, ALogP 3.43, HBA 5, HBD 1, PSA 71.89, QED 0.53
Compound (SMILES): CC(C)Oc1ccc(N2CC[C@]3(CC[C@@](O)(COCCF)CC3)C2=O)cc1
InChIKey: YCNLXCVDSQLZQU-OYRHEFFESA-N
Target: Hormone-sensitive lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q05469
Assay: Enzyme Inhibition Assay: HSL enzyme activity was measured by a colorimetric assay using 2,3-dimercapto-1-propanol tributyrate (Aldrich, St. Louis, Mo.) as a substrate. Typically, 1.5 mM 2,3-dimercapto-1-propanol tributyrate (DMPT) in 100 mM MOPS, pH 7.2, 0.2 mg/ml fatty acid-free BSA was prepared by sonication at 4° C. to homogenous suspension. Test compounds (2 mM stock in DMSO) were diluted 3 fold in series in DMSO. Compound solutions were diluted 24 fold in 1.5 mM DMPT containing solution and 18 ul per well was added to 384-well microplates (Corning Costar). Twelve microliters per well of human HSL (15 ug/ml) was added and the reaction mixture was incubated at 37° C. for 20 minutes. Six microliters of 12 mM dithio-bis-(2-nitrobenzoic acid) (DTNB) in DMSO plus 1.2% SDS and 0.6% Triton X-100 were added and the mixture was incubated at room temperature for 15 minutes.
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 379.47, ALogP 3.49, HBA 4, HBD 1, PSA 59, QED 0.74
Compound (SMILES): CCCNC(=S)c1ccc(-n2ccc3ccccc32)s1
InChIKey: OSMMLDCYRLJBKD-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 459 nM (pChEMBL 6.340000152587891)
Descriptors: MW 300.45, ALogP 4.37, HBA 3, HBD 1, PSA 16.96, QED 0.72
Compound (SMILES): CCCNC(=O)c1ccc(N2CCCCC2)s1
InChIKey: KYRYAIBHJGHRFB-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 252.38, ALogP 2.88, HBA 3, HBD 1, PSA 32.34, QED 0.89
Compound (SMILES): CCCNC(=O)c1ccc(-n2cccn2)s1
InChIKey: SVKULENTQVNTFM-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 235.31, ALogP 2.07, HBA 4, HBD 1, PSA 46.92, QED 0.88
Compound (SMILES): CCCNC(=O)c1ccc(N2CCN(C)CC2)s1
InChIKey: JAWCIYWVQKUFOY-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 267.4, ALogP 1.64, HBA 4, HBD 1, PSA 35.58, QED 0.9
Compound (SMILES): CCCNC(=O)c1ccc(-n2c(C)nc3ccccc32)s1
InChIKey: KBBUJPFPTIFZBX-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 299.4, ALogP 3.54, HBA 4, HBD 1, PSA 46.92, QED 0.8
Compound (SMILES): CCCNC(=O)c1ccc(N2CC(C)Sc3ccccc32)s1
InChIKey: AZPDHDPLHYDWFN-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 19100 nM (pChEMBL 4.71999979019165)
Descriptors: MW 332.49, ALogP 4.52, HBA 4, HBD 1, PSA 32.34, QED 0.89
Compound (SMILES): CCCNC(=O)c1ccc(N2CCSc3ccccc32)s1
InChIKey: OLODXINGXSFYCZ-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 318.47, ALogP 4.13, HBA 4, HBD 1, PSA 32.34, QED 0.92
Compound (SMILES): CCCNC(=O)c1ccc(N2CCOc3ccc(Cl)cc32)s1
InChIKey: YEXYYZPPDQZXAW-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 7500 nM (pChEMBL 5.119999885559082)
Descriptors: MW 336.84, ALogP 4.07, HBA 4, HBD 1, PSA 41.57, QED 0.91
Compound (SMILES): CCCNC(=O)c1ccc(N2CCc3ccccc32)s1
InChIKey: KHAUYLOLWULIBQ-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 286.4, ALogP 3.58, HBA 3, HBD 1, PSA 32.34, QED 0.93
Compound (SMILES): CCCNC(=O)c1ccc(N2CCSc3ncccc32)s1
InChIKey: OJRRZFYDJWKGRZ-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 13800 nM (pChEMBL 4.860000133514404)
Descriptors: MW 319.45, ALogP 3.53, HBA 5, HBD 1, PSA 45.23, QED 0.94
Compound (SMILES): CCCNC(=O)c1ccc(N2Cc3cccc(OC)c3Oc3ncccc32)s1
InChIKey: UOGGHSISKKLHGI-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 395.48, ALogP 4.74, HBA 6, HBD 1, PSA 63.69, QED 0.68
Compound (SMILES): O=C(c1ccc(-n2cnc3ccccc32)s1)N1CCCC1
InChIKey: IAKWLEXUJYDTSV-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 297.38, ALogP 3.32, HBA 4, HBD 0, PSA 38.13, QED 0.73
Compound (SMILES): O=C(NCCO)c1ccc(-n2cnc3ccccc32)s1
InChIKey: ZUENCQULKNYXLX-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 287.34, ALogP 1.81, HBA 5, HBD 2, PSA 67.15, QED 0.77
Compound (SMILES): CCNC(=O)c1ccc(-n2c(C)nc3ccccc32)s1
InChIKey: UZEBSARTLJQKKF-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 191 nM (pChEMBL 6.71999979019165)
Descriptors: MW 285.37, ALogP 3.15, HBA 4, HBD 1, PSA 46.92, QED 0.8
Compound (SMILES): O=C(c1ccc(-n2cnc3ccccc32)s1)N1CCCCC1
InChIKey: MXTJXOJIAYECBI-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 311.41, ALogP 3.71, HBA 4, HBD 0, PSA 38.13, QED 0.72
Compound (SMILES): CC[C@H](C)NC(=O)c1ccc(-n2cnc3ccccc32)s1
InChIKey: XYJQMXDDOWNURL-NSHDSACASA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 17900 nM (pChEMBL 4.75)
Descriptors: MW 299.4, ALogP 3.62, HBA 4, HBD 1, PSA 46.92, QED 0.8
Compound (SMILES): COc1ccc2c(c1)nc(C)n2-c1ccc(C(=O)NC2CC2)s1
InChIKey: MHKAPBXZAFYGFS-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 212 nM (pChEMBL 6.670000076293945)
Descriptors: MW 327.41, ALogP 3.3, HBA 5, HBD 1, PSA 56.15, QED 0.8