lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccccc1CCc1ccnc(NC(N)=O)c1
InChIKey: WJBGFWIEPWCRKP-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 271.32, ALogP 2.37, HBA 3, HBD 2, PSA 77.24, QED 0.88
Compound (SMILES): NC(=O)Nc1cc(CCc2ccccc2F)ccn1
InChIKey: VSSKWKPOZYFECO-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 259.28, ALogP 2.5, HBA 2, HBD 2, PSA 68.01, QED 0.89
Compound (SMILES): NC(=O)Nc1cc(CCc2ccccc2C(F)(F)F)ccn1
InChIKey: FJYVFPUQYHIRKW-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 309.29, ALogP 3.38, HBA 2, HBD 2, PSA 68.01, QED 0.91
Compound (SMILES): NC(=O)Nc1cc(CCc2ccccc2)ccn1
InChIKey: IUJDPFDOZKFDED-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 241.29, ALogP 2.36, HBA 2, HBD 2, PSA 68.01, QED 0.86
Compound (SMILES): COc1ccc(CCc2ccnc(NC(N)=O)c2)cc1
InChIKey: YCMFXFDLDYBLMO-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 271.32, ALogP 2.37, HBA 3, HBD 2, PSA 77.24, QED 0.88
Compound (SMILES): NC(=O)Nc1cc(CCc2ccc(C(F)(F)F)cc2)ccn1
InChIKey: SKMSEHMSEFDKRY-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 309.29, ALogP 3.38, HBA 2, HBD 2, PSA 68.01, QED 0.91
Compound (SMILES): Cc1cc(F)ccc1CCc1ccnc(NC(N)=O)c1
InChIKey: CXKHFDPOIKOCQS-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 273.31, ALogP 2.8, HBA 2, HBD 2, PSA 68.01, QED 0.9
Compound (SMILES): NC(=O)Nc1cc(CCc2ccc(F)c(C(F)(F)F)c2)ccn1
InChIKey: ODRCHWWBMHQWDO-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 327.28, ALogP 3.52, HBA 2, HBD 2, PSA 68.01, QED 0.84
Compound (SMILES): Cn1cnc(-c2ccc(F)cc2)c1-c1ccnc(NC(N)=O)c1
InChIKey: ZIJSGNSFRONJLZ-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 311.32, ALogP 2.78, HBA 4, HBD 2, PSA 85.83, QED 0.78
Compound (SMILES): COc1ccc(Cn2cnc(-c3ccc(F)cc3)c2-c2ccnc(NC(N)=O)c2)c(OC)c1
InChIKey: DTRJSWFYQCDQHO-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 447.47, ALogP 4.31, HBA 6, HBD 2, PSA 104.29, QED 0.44
Compound (SMILES): NC(=O)Nc1cc(-c2nc[nH]c2-c2ccc(F)cc2)ccn1
InChIKey: CYYTVUKCHKHPDX-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 297.29, ALogP 2.77, HBA 3, HBD 3, PSA 96.69, QED 0.69
Compound (SMILES): Cn1cnc(-c2ccnc(NC(N)=O)c2)c1-c1ccc(F)cc1
InChIKey: LOWPEVFPJIIXSD-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 311.32, ALogP 2.78, HBA 4, HBD 2, PSA 85.83, QED 0.78
Compound (SMILES): NC(=O)Nc1cc(-c2ocnc2-c2ccc(F)cc2)ccn1
InChIKey: OQTWCWPFOSBVDI-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 298.28, ALogP 3.03, HBA 4, HBD 2, PSA 94.04, QED 0.78
Compound (SMILES): NC(=O)Nc1cc(N2CCCC2c2ccc(F)cc2)ccn1
InChIKey: JQTDLFVIBXSMQL-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 300.34, ALogP 3.05, HBA 3, HBD 2, PSA 71.25, QED 0.91
Compound (SMILES): NC(=O)Nc1cc(C2=C(c3ccc(F)cc3)CCCC2)ccn1
InChIKey: IDZIQEQJVCRWQF-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 311.36, ALogP 4.2, HBA 2, HBD 2, PSA 68.01, QED 0.89
Compound (SMILES): NC(=O)Nc1cc(C2CCCCC2c2ccc(F)cc2)ccn1
InChIKey: LKJVPQQHOPZTPA-UHFFFAOYSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Competitive Molecular Binding Assay: The MR competitive binding assay is based on the binding and displacement of a TAMRA-labeled Dexamethasone probe with fluorescence polarization (FP) detection. The assay is performed in 384-well, low volume NBS black plates (Corning #3676) in assay buffer consisting of 10 mM TES, pH 7.4, 50 mM KCl, 20 mM Sodium molybdate, 1.5 mM EDTA, 0.04% CHAPS, 10% Glycerol and 1 mM DTT. Full Length human mineralocorticoid receptor (hMR) present in a baculovirus infected insect cell lysate is diluted 2 fold in assay buffer and 10 μL of this dilution is added to the assay plate. Blank wells receive 10 μL of the diluted MR lysate containing 3 μM Dexamethasone. 2 μL diluted test compound is transferred to the assay plate for a final starting top concentration of 10 μM in 1% DMSO. The reaction is started by adding 3 μL of 25 nM probe in assay buffer for a final assay concentration of 5 nM.
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 313.38, ALogP 4.15, HBA 2, HBD 2, PSA 68.01, QED 0.89
Compound (SMILES): CC1(c2ccc(NC(=O)c3ncc(C#N)[nH]3)c(C3=CCCCC3)c2)OCCO1
InChIKey: VIWFELRUSGWYMK-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Mus musculus
UniProt: P09581
Assay: Inhibition of c-FMS in mouse BMDM assessed as reduction in CSF-1 stimulated cell proliferation by measuring BrDU incorporation treated for 30 hrs followed by BrDU addition during last 6 hrs of incubation by ELISA
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 378.43, ALogP 3.71, HBA 5, HBD 2, PSA 100.03, QED 0.84
Compound (SMILES): CC1(c2ccc(NC(=O)c3ncc(C#N)[nH]3)c(C3=CCCCC3)c2)OCCCO1
InChIKey: VAJNHEUOIQZVIF-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Mus musculus
UniProt: P09581
Assay: Fluorescence Polarization Competition Immunoassay: An autophosphorylation, fluorescence polarization competition immunoassay was used to determine the potency for c-fms inhibition exhibited by selected compounds of Formula I. The assay was performed in black 96-well microplates (LJL BioSystems). The assay buffer used was 100 mM 4-(2-hydroxyethyl)piperazine 1-ethanesulfonic acid (HEPES), pH 7.5, 1 mM 1,4-dithio-DL-threitol (DTT), 0.01% (v/v) Tween-20. Compounds were diluted in assay buffer containing 4% dimethylsulfoxide (DMSO) just prior to the assay. To each well, 5 μL of compound were added followed by the addition of 3 μL of a mix containing 33 nM c-fms (Johnson & Johnson PRD) and 16.7 mM MgCl2 (Sigma) in assay buffer. The kinase reaction was initiated by adding 2 μL of 5 mM ATP (Sigma) in assay buffer. The final concentrations in the assay were 10 nM c-fms, 1 mM ATP, 5 mM MgCl2, 2% DMSO.
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 392.46, ALogP 4.1, HBA 5, HBD 2, PSA 100.03, QED 0.82
Compound (SMILES): CCC[C@@H]1C[C@@]2(CC[C@H]1O)CCN(c1ccc(OC(F)(F)F)cc1)C2=O
InChIKey: CRLYLLMVSJJPLT-MZMPZRCHSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 371.4, ALogP 4.27, HBA 3, HBD 1, PSA 49.77, QED 0.86
Compound (SMILES): CC(C)[C@@H]1C[C@@]2(CC[C@H]1O)CCN(c1ccc(OC(F)(F)F)cc1)C2=O
InChIKey: NLHHYKJVMWXELZ-LZLYRXPVSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 16.2 nM (pChEMBL 7.789999961853027)
Descriptors: MW 371.4, ALogP 4.13, HBA 3, HBD 1, PSA 49.77, QED 0.87
Compound (SMILES): CC(C)O[C@@H]1C[C@@]2(CC[C@H]1O)CCN(c1ccc(OC(F)(F)F)cc1)C2=O
InChIKey: HNTWSIJLQIMPBZ-JFIYKMOQSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 387.4, ALogP 3.65, HBA 4, HBD 1, PSA 59, QED 0.86
Compound (SMILES): CCO[C@@H]1C[C@@]2(CC[C@H]1O)CCN(c1ccc(OC(F)(F)F)cc1)C2=O
InChIKey: JNJPMTLZSXBHIJ-BFYDXBDKSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 198 nM (pChEMBL 6.699999809265137)
Descriptors: MW 373.37, ALogP 3.26, HBA 4, HBD 1, PSA 59, QED 0.88
Compound (SMILES): O=C1N(c2ccc(OC(F)(F)F)cc2)CC[C@@]12CC[C@@H](O)[C@H](OCC(F)(F)F)C2
InChIKey: PPWLUVUZMIXMJC-IIAWOOMASA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 66.4 nM (pChEMBL 7.179999828338623)
Descriptors: MW 427.34, ALogP 3.8, HBA 4, HBD 1, PSA 59, QED 0.74
Compound (SMILES): CO[C@@H]1C[C@@]2(CC[C@H]1O)CCN(c1ccc(OC(F)(F)F)cc1)C2=O
InChIKey: SUYFLKVYVRWKMI-IIAWOOMASA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 343 nM (pChEMBL 6.460000038146973)
Descriptors: MW 359.34, ALogP 2.87, HBA 4, HBD 1, PSA 59, QED 0.9
Compound (SMILES): CCCO[C@@H]1C[C@@]2(CC[C@H]1O)CCN(c1ccc(OC(F)(F)F)cc1)C2=O
InChIKey: PTGRKADUKRSWIA-JFIYKMOQSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 73.3 nM (pChEMBL 7.130000114440918)
Descriptors: MW 387.4, ALogP 3.65, HBA 4, HBD 1, PSA 59, QED 0.84
Compound (SMILES): CCC[C@@H]1C[C@@]2(CC[C@H]1O)CCN(c1ccc(OCC(F)(F)F)cc1)C2=O
InChIKey: QGVFVHFQCBELNT-LSBZLQRGSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 385.43, ALogP 4.31, HBA 3, HBD 1, PSA 49.77, QED 0.82
Compound (SMILES): CC(C)[C@@H]1C[C@@]2(CC[C@H]1O)CCN(c1ccc(OCC(F)(F)F)cc1)C2=O
InChIKey: BGHKCNHEBSHENM-YQVWRLOYSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 385.43, ALogP 4.17, HBA 3, HBD 1, PSA 49.77, QED 0.85
Compound (SMILES): O=C1N(c2ccc(OCC(F)(F)F)cc2)CC[C@@]12CC[C@@H](O)[C@H](OCC(F)(F)F)C2
InChIKey: ZYNDZSWTZGGJGC-BFYDXBDKSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 441.37, ALogP 3.84, HBA 4, HBD 1, PSA 59, QED 0.71
Compound (SMILES): CCO[C@@H]1C[C@@]2(CC[C@H]1O)CCN(c1ccc(OCC(F)(F)F)cc1)C2=O
InChIKey: DHPMSQPFKXIQSS-JFIYKMOQSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 994 nM (pChEMBL 6)
Descriptors: MW 387.4, ALogP 3.3, HBA 4, HBD 1, PSA 59, QED 0.84
Compound (SMILES): CC(C)O[C@@H]1C[C@@]2(CC[C@H]1O)CCN(c1ccc(OCC(F)(F)F)cc1)C2=O
InChIKey: TWYXVYSMMUCKOW-ZHALLVOQSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 422 nM (pChEMBL 6.380000114440918)
Descriptors: MW 401.43, ALogP 3.69, HBA 4, HBD 1, PSA 59, QED 0.82
Compound (SMILES): CO[C@H](c1ccc(N2CC[C@@]3(CC[C@@H](O)[C@H](OC(C)C)C3)C2=O)cc1)C(F)(F)F
InChIKey: UISKTUYIECGCNM-SOAMZJECSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 136 nM (pChEMBL 6.869999885559082)
Descriptors: MW 415.45, ALogP 4, HBA 4, HBD 1, PSA 59, QED 0.79
Compound (SMILES): CO[C@H](c1ccc(N2CC[C@@]3(CC[C@@H](O)[C@H](OCC(F)(F)F)C3)C2=O)cc1)C(F)(F)F
InChIKey: YZTKPBAXESIKIE-YFHUEUNASA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 455.39, ALogP 4.15, HBA 4, HBD 1, PSA 59, QED 0.68
Compound (SMILES): O=C1N(c2ccc([C@@H](OCc3ccccc3)C(F)(F)F)cc2)CC[C@@]12CC[C@@H](O)[C@H](OCC(F)(F)F)C2
InChIKey: SYPRGLCEKGZXFH-GBEXAXCTSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 1067 nM (pChEMBL 5.96999979019165)
Descriptors: MW 531.49, ALogP 5.72, HBA 4, HBD 1, PSA 59, QED 0.46
Compound (SMILES): O=C1N(c2ccc([C@@H](O)C(F)(F)F)cc2)CC[C@@]12CC[C@@H](O)[C@H](OCC(F)(F)F)C2
InChIKey: IJQQUSSCHHFEGJ-KCYZZUKISA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 185 nM (pChEMBL 6.730000019073486)
Descriptors: MW 441.37, ALogP 3.5, HBA 4, HBD 2, PSA 70, QED 0.7
Compound (SMILES): O=C1N(c2ccc(OC(F)(F)F)cc2)CC[C@]12CC[C@H](O)[C@@H](OCC(F)(F)F)C2
InChIKey: PPWLUVUZMIXMJC-DZKIICNBSA-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. Product production was monitored by reading absorbance at 405 nm on an Envision Reader.
Measurement: IC50 = 42.1 nM (pChEMBL 7.380000114440918)
Descriptors: MW 427.34, ALogP 3.8, HBA 4, HBD 1, PSA 59, QED 0.74
Compound (SMILES): CN(CCCNC(=O)Nc1ccc(C(C)(C)C)cc1)CC1O[C@@H](n2ccc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: SXZVJXPNQRTMDB-VIMIFYJLSA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Biochemical Assay: Compound was serially diluted 3 fold in DMSO for 10 points and 1 μl was plated in a 384 well microtiter plate. Positive control (100% inhibition standard) was 2.5 uM final concentration of S-adenosyl-L-homocysteine and negative control (0% inhibition standard) contained 1 μl of DMSO. Compound was then incubated for 30 minutes with 40 μl per well of DOT1L(1-416) (0.25 nM final concentration in assay buffer: 20 mM TRIS, pH 8.0, 10 mM NaCl, 0.002% Tween20, 0.005% Bovine Skin Gelatin, 100 mM KCl, and 0.5 mM DTT). 10 μl per well of substrate mix (same assay buffer with 200 nM S-[methyl-3H]-adenosyl-L methionine, 600 nM of unlabeled S-[methyl-3H]-adenosyl-L methionine, and 20 nM oligonucleosome) was added to initiate the reaction. Reaction was incubated for 120 minutes at room temperature and quenched with 10 μl per well of 100 μM S-methyl-adenosyl-L methionine.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 511.63, ALogP 2.07, HBA 9, HBD 5, PSA 150.79, QED 0.29
Compound (SMILES): CC(C)N(CCCNC(=O)Nc1ccc(C(C)(C)C)cc1)CC1O[C@@H](n2ccc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: WXRGFPHDRFQODR-KYSCMSHESA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Biochemical Assay: Compound was serially diluted 3 fold in DMSO for 10 points and 1 μl was plated in a 384 well microtiter plate. Positive control (100% inhibition standard) was 2.5 uM final concentration of S-adenosyl-L-homocysteine and negative control (0% inhibition standard) contained 1 μl of DMSO. Compound was then incubated for 30 minutes with 40 μl per well of DOT1L(1-416) (0.25 nM final concentration in assay buffer: 20 mM TRIS, pH 8.0, 10 mM NaCl, 0.002% Tween20, 0.005% Bovine Skin Gelatin, 100 mM KCl, and 0.5 mM DTT). 10 μl per well of substrate mix (same assay buffer with 200 nM S-[methyl-3H]-adenosyl-L methionine, 600 nM of unlabeled S-[methyl-3H]-adenosyl-L methionine, and 20 nM oligonucleosome) was added to initiate the reaction. Reaction was incubated for 120 minutes at room temperature and quenched with 10 μl per well of 100 μM S-methyl-adenosyl-L methionine.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 539.68, ALogP 2.85, HBA 9, HBD 5, PSA 150.79, QED 0.26
Compound (SMILES): CC(C)N(CCCNC(=O)Nc1nc2ccc(C(C)(C)C)cc2[nH]1)CC1O[C@@H](n2ccc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: JHPZZWSSEJCBRJ-KYSCMSHESA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Biochemical Assay: Compound was serially diluted 3 fold in DMSO for 10 points and 1 μl was plated in a 384 well microtiter plate. Positive control (100% inhibition standard) was 2.5 uM final concentration of S-adenosyl-L-homocysteine and negative control (0% inhibition standard) contained 1 μl of DMSO. Compound was then incubated for 30 minutes with 40 μl per well of DOT1L(1-416) (0.25 nM final concentration in assay buffer: 20 mM TRIS, pH 8.0, 10 mM NaCl, 0.002% Tween20, 0.005% Bovine Skin Gelatin, 100 mM KCl, and 0.5 mM DTT). 10 μl per well of substrate mix (same assay buffer with 200 nM S-[methyl-3H]-adenosyl-L methionine, 600 nM of unlabeled S-[methyl-3H]-adenosyl-L methionine, and 20 nM oligonucleosome) was added to initiate the reaction. Reaction was incubated for 120 minutes at room temperature and quenched with 10 μl per well of 100 μM S-methyl-adenosyl-L methionine.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 579.71, ALogP 2.73, HBA 10, HBD 6, PSA 179.47, QED 0.16
Compound (SMILES): CC(C)(C)c1ccc(NC(=O)NCCCNC[C@@H]2O[C@H](n3ccc4c(N)ncnc43)[C@@H](O)[C@H]2O)cc1
InChIKey: SOMJJYYPSTVHMN-MXBUBSDBSA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Biochemical Assay: Compound was serially diluted 3 fold in DMSO for 10 points and 1 μl was plated in a 384 well microtiter plate. Positive control (100% inhibition standard) was 2.5 uM final concentration of S-adenosyl-L-homocysteine and negative control (0% inhibition standard) contained 1 μl of DMSO. Compound was then incubated for 30 minutes with 40 μl per well of DOT1L(1-416) (0.25 nM final concentration in assay buffer: 20 mM TRIS, pH 8.0, 10 mM NaCl, 0.002% Tween20, 0.005% Bovine Skin Gelatin, 100 mM KCl, and 0.5 mM DTT). 10 μl per well of substrate mix (same assay buffer with 200 nM S-[methyl-3H]-adenosyl-L methionine, 600 nM of unlabeled S-[methyl-3H]-adenosyl-L methionine, and 20 nM oligonucleosome) was added to initiate the reaction. Reaction was incubated for 120 minutes at room temperature and quenched with 10 μl per well of 100 μM S-methyl-adenosyl-L methionine.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 497.6, ALogP 1.73, HBA 9, HBD 6, PSA 159.58, QED 0.26