lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(CN[C@H]2CC2c2ccccc2)cc1Cl
InChIKey: PKPAFGXQEMVOHI-WMCAAGNKSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 9800 nM (pChEMBL 5.010000228881836)
Descriptors: MW 287.79, ALogP 3.99, HBA 2, HBD 1, PSA 21.26, QED 0.9
Compound (SMILES): COc1ccc(CN[C@H]2CC2c2ccccc2)cc1F
InChIKey: OPSGFELBTCGXLT-WMCAAGNKSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 271.34, ALogP 3.48, HBA 2, HBD 1, PSA 21.26, QED 0.9
Compound (SMILES): COc1ccc(CN[C@H]2CC2c2ccccc2)c(C)c1
InChIKey: FRNCSCKKYQHEDU-ZVAWYAOSSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 13800 nM (pChEMBL 4.860000133514404)
Descriptors: MW 267.37, ALogP 3.65, HBA 2, HBD 1, PSA 21.26, QED 0.89
Compound (SMILES): c1ccc(C2C[C@@H]2NCc2cccc3c2OCCCO3)cc1
InChIKey: JYFAAFPPBXCACB-DJNXLDHESA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 26600 nM (pChEMBL 4.579999923706055)
Descriptors: MW 295.38, ALogP 3.49, HBA 3, HBD 1, PSA 30.49, QED 0.94
Compound (SMILES): c1ccc(C2C[C@@H]2NCc2ccc3c(c2)OCCCO3)cc1
InChIKey: XWILQZPMMYRPQW-DJNXLDHESA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 295.38, ALogP 3.49, HBA 3, HBD 1, PSA 30.49, QED 0.94
Compound (SMILES): CC1(C)CCc2cc(CN[C@H]3CC3c3ccccc3)ccc2O1
InChIKey: BWFVRZZEYZEBLZ-GGYWPGCISA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 307.44, ALogP 4.44, HBA 2, HBD 1, PSA 21.26, QED 0.9
Compound (SMILES): COc1ccc(CN[C@H]2CC2c2ccccc2)c(C)c1C
InChIKey: ABOKCGLYBDRXTG-ZVAWYAOSSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 25300 nM (pChEMBL 4.599999904632568)
Descriptors: MW 281.4, ALogP 3.96, HBA 2, HBD 1, PSA 21.26, QED 0.9
Compound (SMILES): COc1cc(C)c(CN[C@H]2CC2c2ccccc2)cc1C
InChIKey: ROWMZQIEORWNAH-ZVAWYAOSSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 23800 nM (pChEMBL 4.619999885559082)
Descriptors: MW 281.4, ALogP 3.96, HBA 2, HBD 1, PSA 21.26, QED 0.9
Compound (SMILES): COc1cc(F)c(CN[C@H]2CC2c2ccccc2)cc1OC
InChIKey: YTWOUSLXHWPROD-WMCAAGNKSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Amplex Red Peroxide/Peroxidase-Coupled Assay: The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc. In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Millipore) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H2O2 produced during the catalytic process, using the Amplex Red peroxide/peroxidase-coupled assay kit (Invitrogen).Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of various concentrations of inhibitor (from 0 to 75 uM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in triplicate.
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 301.36, ALogP 3.49, HBA 3, HBD 1, PSA 30.49, QED 0.89
Compound (SMILES): COc1cc(CN[C@H]2CC2c2ccccc2)cc(Cl)c1OC
InChIKey: BIPUKHTVGDBASI-WMCAAGNKSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Amplex Red Peroxide/Peroxidase-Coupled Assay: The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc. In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Millipore) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H2O2 produced during the catalytic process, using the Amplex Red peroxide/peroxidase-coupled assay kit (Invitrogen).Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of various concentrations of inhibitor (from 0 to 75 uM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in triplicate.
Measurement: IC50 = 147 nM (pChEMBL 6.829999923706055)
Descriptors: MW 317.82, ALogP 4, HBA 3, HBD 1, PSA 30.49, QED 0.87
Compound (SMILES): COc1ccc(CN[C@H]2CC2c2ccccc2)c(Cl)c1OC
InChIKey: RKGHQTUIBYROBN-LOACHALJSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 317.82, ALogP 4, HBA 3, HBD 1, PSA 30.49, QED 0.87
Compound (SMILES): c1ccc(C2C[C@@H]2NCc2ccc3[nH]ccc3c2)cc1
InChIKey: OSJXBBPQFCCQIW-DAFXYXGESA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 262.36, ALogP 3.81, HBA 1, HBD 2, PSA 27.82, QED 0.73
Compound (SMILES): c1ccc(COc2ccc(C3C[C@@H]3NCc3ccccn3)cc2)cc1
InChIKey: PUKPTRPSSAXMPI-KEKNWZKVSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 330.43, ALogP 4.31, HBA 3, HBD 1, PSA 34.15, QED 0.7
Compound (SMILES): COc1ccccc1CN[C@H]1CC1c1ccc(OCc2ccccc2)cc1
InChIKey: PPCBJIQRKKFFJQ-WCSIJFPASA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 359.47, ALogP 4.92, HBA 3, HBD 1, PSA 30.49, QED 0.62
Compound (SMILES): COc1ccc(C(C)N[C@H]2CC2c2ccccc2)cc1
InChIKey: AYWVGPXQTYCBNI-SYGMWZTRSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Amplex Red Peroxide/Peroxidase-Coupled Assay: The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc. In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Millipore) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H2O2 produced during the catalytic process, using the Amplex Red peroxide/peroxidase-coupled assay kit (Invitrogen).Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of various concentrations of inhibitor (from 0 to 75 uM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in triplicate.
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 267.37, ALogP 3.9, HBA 2, HBD 1, PSA 21.26, QED 0.89
Compound (SMILES): COc1ccc(C(C)N[C@H]2CC2c2ccccc2)cc1OC
InChIKey: ONADIUZVFCLIBW-IMRCBTMISA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Amplex Red Peroxide/Peroxidase-Coupled Assay: The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc. In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Millipore) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H2O2 produced during the catalytic process, using the Amplex Red peroxide/peroxidase-coupled assay kit (Invitrogen).Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of various concentrations of inhibitor (from 0 to 75 uM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in triplicate.
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 297.4, ALogP 3.91, HBA 3, HBD 1, PSA 30.49, QED 0.88
Compound (SMILES): CC(N[C@H]1CC1c1ccccc1)c1ccc2c(c1)OCCO2
InChIKey: PAXGPAVOMLKKDQ-IMRCBTMISA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 7400 nM (pChEMBL 5.130000114440918)
Descriptors: MW 295.38, ALogP 3.66, HBA 3, HBD 1, PSA 30.49, QED 0.93
Compound (SMILES): COc1ccc(CC(C)N[C@H]2CC2c2ccccc2)cc1OC
InChIKey: FZKMYHFPTZQCSK-UYJHFMRCSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 311.43, ALogP 3.78, HBA 3, HBD 1, PSA 30.49, QED 0.84
Compound (SMILES): Cc1noc(CN[C@H]2CC2c2ccccc2)n1
InChIKey: UCOWFDFKHOLJNS-KIYNQFGBSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 38000 nM (pChEMBL 4.420000076293945)
Descriptors: MW 229.28, ALogP 2.02, HBA 4, HBD 1, PSA 50.95, QED 0.87
Compound (SMILES): C[Si](C)(C)C1=C2c3nc4ccccc4cc3C(O)CC2CC1=O
InChIKey: OIIOPIIGGQSDJQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Enzyme Inhibition Assay: The tests are carried out as follows: the enzyme to be assayed was purified, for example by affinity chromatography on agarose beads. The catalytic activity was measured using radiolabeled ATP, at a standard final concentration. The test compounds were added at various concentrations making it possible to establish dose-response curves (activity of the enzyme as a function of the concentration).
Measurement: IC50 = 1950 nM (pChEMBL 5.710000038146973)
Descriptors: MW 323.47
Compound (SMILES): C[Si](C)(C)C1=C2c3nc4ccccc4cc3C(Cl)CC2CC1=O
InChIKey: FVCLWQFXKORWCH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Enzyme Inhibition Assay: The tests are carried out as follows: the enzyme to be assayed was purified, for example by affinity chromatography on agarose beads. The catalytic activity was measured using radiolabeled ATP, at a standard final concentration. The test compounds were added at various concentrations making it possible to establish dose-response curves (activity of the enzyme as a function of the concentration).
Measurement: IC50 = 63000 nM (pChEMBL 4.199999809265137)
Descriptors: MW 341.91
Compound (SMILES): COc1ccc2nc3c(cc2c1)C(O)CC1CC(=O)C([Si](C)(C)C)=C31
InChIKey: GPLFVGIGKBFDJY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Enzyme Inhibition Assay: The tests are carried out as follows: the enzyme to be assayed was purified, for example by affinity chromatography on agarose beads. The catalytic activity was measured using radiolabeled ATP, at a standard final concentration. The test compounds were added at various concentrations making it possible to establish dose-response curves (activity of the enzyme as a function of the concentration).
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 353.49
Compound (SMILES): COc1ccc2cc3c(nc2c1)C1=C([Si](C)(C)C)C(=O)CC1CC3O
InChIKey: LLFGZHHEIQWCBU-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Enzyme Inhibition Assay: The tests are carried out as follows: the enzyme to be assayed was purified, for example by affinity chromatography on agarose beads. The catalytic activity was measured using radiolabeled ATP, at a standard final concentration. The test compounds were added at various concentrations making it possible to establish dose-response curves (activity of the enzyme as a function of the concentration).
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 353.49
Compound (SMILES): COc1cc2cc3c(nc2cc1OC)C1=C([Si](C)(C)C)C(=O)CC1CC3O
InChIKey: JAXIMGVTBDOXDU-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Enzyme Inhibition Assay: The tests are carried out as follows: the enzyme to be assayed was purified, for example by affinity chromatography on agarose beads. The catalytic activity was measured using radiolabeled ATP, at a standard final concentration. The test compounds were added at various concentrations making it possible to establish dose-response curves (activity of the enzyme as a function of the concentration).
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 383.52
Compound (SMILES): O=C(NC1CNCCC1c1cccc(F)c1)c1ccc2[nH]nc(-c3ccncc3)c2c1
InChIKey: HGSIQHLBRZODEA-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 415.47, ALogP 3.64, HBA 4, HBD 3, PSA 82.7, QED 0.48
Compound (SMILES): O=C(NC1CCCCNC1=O)c1ccc2[nH]nc(-c3ccncc3)c2c1
InChIKey: AMFJMDIQTRSKQE-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 349.39, ALogP 2.02, HBA 4, HBD 3, PSA 99.77, QED 0.67
Compound (SMILES): O=C(NC1CN(C(=O)OCc2ccccc2)CCNC1=O)c1ccc2[nH]nc(-c3ccncc3)c2c1
InChIKey: AXJMXQMYKLUCIH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 484.52, ALogP 2.49, HBA 6, HBD 3, PSA 129.31, QED 0.4
Compound (SMILES): O=C(N[C@@H]1CCCN(Cc2ccccc2F)C1)c1ccc2[nH]nc(-c3ccnc(Cl)c3)c2c1
InChIKey: CKPMDMZGNPFCCQ-LJQANCHMSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 0.58 nM (pChEMBL 9.239999771118164)
Descriptors: MW 463.94, ALogP 4.81, HBA 4, HBD 2, PSA 73.91, QED 0.42
Compound (SMILES): CC(C)Oc1ccc(-c2n[nH]c3ccc(C(=O)N[C@@H]4CCCN(Cc5ccccc5F)C4)cc23)cc1
InChIKey: CCSBRKICEAUMTP-HSZRJFAPSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 486.59, ALogP 5.55, HBA 4, HBD 2, PSA 70.25, QED 0.36
Compound (SMILES): CC(C)Oc1ccc(-c2n[nH]c3ccc(C(=O)N[C@@H]4CCCN(Cc5ccccc5F)C4)cc23)cn1
InChIKey: OERGTYGYDNZDQC-JOCHJYFZSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 487.58, ALogP 4.95, HBA 5, HBD 2, PSA 83.14, QED 0.39
Compound (SMILES): O=C(N[C@@H]1CCCN(Cc2ccccc2F)C1)c1ccc2[nH]nc(-c3ccc4c(c3)CCO4)c2c1
InChIKey: NGLSLPSSSLAXOR-JOCHJYFZSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 0.61 nM (pChEMBL 9.210000038146973)
Descriptors: MW 470.55, ALogP 4.7, HBA 4, HBD 2, PSA 70.25, QED 0.44
Compound (SMILES): COc1cccc(F)c1CN1CCC[C@@H](NC(=O)c2ccc3[nH]nc(C4=CCOCC4)c3c2)C1
InChIKey: ICSYSVGTZHQMRP-LJQANCHMSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 464.54, ALogP 3.91, HBA 5, HBD 2, PSA 79.48, QED 0.58
Compound (SMILES): COc1cccc(F)c1CN1CCC[C@@H](NC(=O)c2ccc3[nH]nc(C4=CCS(=O)(=O)CC4)c3c2)C1
InChIKey: PKYGRAZBKUKUNR-LJQANCHMSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 8.4 nM (pChEMBL 8.079999923706055)
Descriptors: MW 512.61, ALogP 3.31, HBA 6, HBD 2, PSA 104.39, QED 0.53
Compound (SMILES): COc1cccc(F)c1CN1CCC[C@@H](NC(=O)c2ccc3[nH]nc(C4CCOCC4)c3c2)C1
InChIKey: PBIQTUVJVOHWAF-LJQANCHMSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: IMAP-FP Assay: Condition 2: Activated ERK2 activity was determined in an IMAP-FP assay (Molecular Devices). Using this assay format, the potency (IC50) of each compound was determined from a 10 point (1:3 serial dilution, 3 uM starting compound concentration) titration curve using the following outlined procedure. 7.5 mL of compound (3333 fold dilution in final assay volume of 25 uL) was added to 15 uL of kinase buffer containing 0.0133 ng/mL (0.316 nM) of fully phosphorylated, mouse aERK2 enzyme. Following a 15 minute incubation, each reaction was initiated by the addition of 10 uL kinase buffer containing 2.45 uM ERK2 IMAP substrate peptides (2.25 uM-unlabeled IPTTPITTTYFFFK-COOH and 200 nM-labeled IPTTPITTTYFFFK-5FAM (5-carboxyfluorescein)-COOH), and 75 uM ATP. The final reaction in each well of 25 uL consists of 0.19 nM mouse ERK2, 900 nM unlabeled peptide, 80 nM labeled-peptide, and 30 uM ATP. Phosphorylation reactions were allowed to proceed for 40-45 minutes.
Measurement: IC50 = 195 nM (pChEMBL 6.710000038146973)
Descriptors: MW 466.56, ALogP 4, HBA 5, HBD 2, PSA 79.48, QED 0.57
Compound (SMILES): O=C(Nc1ccc2[nH]nc(-c3ccncc3)c2c1)C1CNCC(c2ccccc2)C1
InChIKey: BZUGAUBVFGCRLX-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 397.48, ALogP 3.96, HBA 4, HBD 3, PSA 82.7, QED 0.49
Compound (SMILES): O=C(NC1CNCC(c2ccccc2)C1)c1ccc2[nH]nc(-c3ccncc3)c2c1
InChIKey: BVNPXPSCNHSCLJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 397.48, ALogP 3.5, HBA 4, HBD 3, PSA 82.7, QED 0.49
Compound (SMILES): O=C(N[C@H]1CCCN(Cc2ccccc2)C1)c1ccc2[nH]nc(-c3ccncc3)c2c1
InChIKey: RJCLUDCGUNLXRQ-NRFANRHFSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 411.51, ALogP 4.02, HBA 4, HBD 2, PSA 73.91, QED 0.52
Compound (SMILES): O=C(N[C@H]1CCCN(Cc2ccccc2F)C1)c1ccc2[nH]nc(-c3ccncc3)c2c1
InChIKey: NWDKBBCVWYJPGV-FQEVSTJZSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q63844
Assay: Temperature Dependence Fluorescence Assay (TdF): The SAR (Structure Activity Relationship) for ERK ligands covered by this invention was interrogated using the TdF (Temperature Dependence Fluorescence) assay or best known as thermal shift assay [1]. The TdF assay was mainly conducted in the 96-well based CHROMO-4 real time fluorescence plate reader (BioRad). The Sypro Orange (Sigma-Aldrich), environmentally sensitive fluorescence dye, was used to monitor the protein folding-unfolding transition. Protein-ligand binding was gauged by the change (or shift) in the unfolding transition temperature (DTm) acquired at protein alone with respect to protein in the presence of ligand of interest.Compound of interest was first prepared in DMSO stock (typical concentration: 10 mM). Sample of 20 uL was then added into the 96-well PCR plate, where it consisted of 3 uM ERK protein and 15, 50 or 100 uM compound (depending on compound's solubility) in buffer (25 mM HEPES, 150 mM NaCl, pH=7.5 and 1 mM DTT).
Measurement: Kd = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 429.5, ALogP 4.16, HBA 4, HBD 2, PSA 73.91, QED 0.5