lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=S(=O)(Nc1cncc(-c2ccc3ncnc(OC4CCOCC4)c3n2)c1)c1ccccc1
InChIKey: DFQOZTRZCLZDHI-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Competitive Assay: The PI3 Kinase Activity/Inhibitor Assay is a competitive assay used for the fast and sensitive quantitation of activity of the four class I PI3 kinases (p110 α, β, γ, δ). The PI3 Kinase Activity/Inhibitor Assay works on the principle that PI3 Kinase phosphorylates P1(3,4)P2 (PIP2), converting it to PI(3,4,5)P3 (PIP3). The PH domain of the protein GRP-1 binds PIP3 with high affinity and specificity. The kit includes this recombinant protein that is used as the capture protein. This protein binds to the glutathione plate and captures either the PIP3 generated as part of the kinase reaction or the biotinylated-PIP3 tracer included in the kit. The captured biotinylated-PIP3 is detected using streptavidin-HRP conjugate and a colorimetric read out (OD 450). The lower the signal, the higher the PI3 Kinase activity.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 463.52, ALogP 3.45, HBA 8, HBD 1, PSA 116.19, QED 0.46
Compound (SMILES): O=S(=O)(Nc1cc(-c2ccc3ncnc(OC4CCOCC4)c3n2)cnc1Cl)c1ccc(F)cc1F
InChIKey: PEHVSVSYATZDNB-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Competitive Assay: The PI3 Kinase Activity/Inhibitor Assay is a competitive assay used for the fast and sensitive quantitation of activity of the four class I PI3 kinases (p110 α, β, γ, δ). The PI3 Kinase Activity/Inhibitor Assay works on the principle that PI3 Kinase phosphorylates P1(3,4)P2 (PIP2), converting it to PI(3,4,5)P3 (PIP3). The PH domain of the protein GRP-1 binds PIP3 with high affinity and specificity. The kit includes this recombinant protein that is used as the capture protein. This protein binds to the glutathione plate and captures either the PIP3 generated as part of the kinase reaction or the biotinylated-PIP3 tracer included in the kit. The captured biotinylated-PIP3 is detected using streptavidin-HRP conjugate and a colorimetric read out (OD 450). The lower the signal, the higher the PI3 Kinase activity.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 533.94, ALogP 4.38, HBA 8, HBD 1, PSA 116.19, QED 0.36
Compound (SMILES): CN1CCC(Oc2ncnc3ccc(-c4cnc(Cl)c(NS(=O)(=O)c5ccc(F)cc5F)c4)nc23)CC1
InChIKey: AYXNKGOCZQARJK-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P27986
Assay: Competitive Assay: The PI3 Kinase Activity/Inhibitor Assay is a competitive assay used for the fast and sensitive quantitation of activity of the four class I PI3 kinases (p110 α, β, γ, δ). The PI3 Kinase Activity/Inhibitor Assay works on the principle that PI3 Kinase phosphorylates P1(3,4)P2 (PIP2), converting it to PI(3,4,5)P3 (PIP3). The PH domain of the protein GRP-1 binds PIP3 with high affinity and specificity. The kit includes this recombinant protein that is used as the capture protein. This protein binds to the glutathione plate and captures either the PIP3 generated as part of the kinase reaction or the biotinylated-PIP3 tracer included in the kit. The captured biotinylated-PIP3 is detected using streptavidin-HRP conjugate and a colorimetric read out (OD 450). The lower the signal, the higher the PI3 Kinase activity.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 546.99, ALogP 4.29, HBA 8, HBD 1, PSA 110.2, QED 0.36
Compound (SMILES): CN1CCC(Oc2ncnc3ccc(-c4cncc(NS(=O)(=O)c5ccccc5)c4)nc23)CC1
InChIKey: VVXLKTAOIWKRIT-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Competitive Assay: The PI3 Kinase Activity/Inhibitor Assay is a competitive assay used for the fast and sensitive quantitation of activity of the four class I PI3 kinases (p110 α, β, γ, δ). The PI3 Kinase Activity/Inhibitor Assay works on the principle that PI3 Kinase phosphorylates P1(3,4)P2 (PIP2), converting it to PI(3,4,5)P3 (PIP3). The PH domain of the protein GRP-1 binds PIP3 with high affinity and specificity. The kit includes this recombinant protein that is used as the capture protein. This protein binds to the glutathione plate and captures either the PIP3 generated as part of the kinase reaction or the biotinylated-PIP3 tracer included in the kit. The captured biotinylated-PIP3 is detected using streptavidin-HRP conjugate and a colorimetric read out (OD 450). The lower the signal, the higher the PI3 Kinase activity.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 476.56, ALogP 3.36, HBA 8, HBD 1, PSA 110.2, QED 0.45
Compound (SMILES): O=S(=O)(Nc1cc(-c2ccc3ncnc(NC4CCOCC4)c3n2)cnc1Cl)c1ccc(F)cc1F
InChIKey: FGVFKGACELNWGS-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Competitive Assay: The PI3 Kinase Activity/Inhibitor Assay is a competitive assay used for the fast and sensitive quantitation of activity of the four class I PI3 kinases (p110 α, β, γ, δ). The PI3 Kinase Activity/Inhibitor Assay works on the principle that PI3 Kinase phosphorylates P1(3,4)P2 (PIP2), converting it to PI(3,4,5)P3 (PIP3). The PH domain of the protein GRP-1 binds PIP3 with high affinity and specificity. The kit includes this recombinant protein that is used as the capture protein. This protein binds to the glutathione plate and captures either the PIP3 generated as part of the kinase reaction or the biotinylated-PIP3 tracer included in the kit. The captured biotinylated-PIP3 is detected using streptavidin-HRP conjugate and a colorimetric read out (OD 450). The lower the signal, the higher the PI3 Kinase activity.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 532.96, ALogP 4.41, HBA 8, HBD 2, PSA 118.99, QED 0.35
Compound (SMILES): Cn1cc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)cn1
InChIKey: NJUKVCLHVLPDAP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 335.34, ALogP 2.66, HBA 6, HBD 2, PSA 85.83, QED 0.77
Compound (SMILES): Nc1sc(-c2c(F)cccc2F)nc1C(=O)Nc1cn[nH]c1N1CCC[C@H](N)C1
InChIKey: NVTPYRCDKQXUGU-VIFPVBQESA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 4.89 nM (pChEMBL 8.3100004196167)
Descriptors: MW 419.46, ALogP 2.57, HBA 7, HBD 4, PSA 125.95, QED 0.51
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1NCC1CCNCC1
InChIKey: QVHWRVHLJFUJKP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 4.54 nM (pChEMBL 8.34000015258789)
Descriptors: MW 447.52, ALogP 3.07, HBA 8, HBD 4, PSA 109.89, QED 0.46
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3ccccc3F)sc2N)c1N1CCC[C@H](N)C1
InChIKey: OEPCHHARAQRIEP-NSHDSACASA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 20.1 nM (pChEMBL 7.699999809265137)
Descriptors: MW 415.5, ALogP 2.44, HBA 8, HBD 3, PSA 115.09, QED 0.6
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3ccccc3)ccc2N)c1N1CCC(N)CC1
InChIKey: CDPLNEIWXMADGF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 41.1 nM (pChEMBL 7.389999866485596)
Descriptors: MW 391.48, ALogP 2.24, HBA 7, HBD 3, PSA 115.09, QED 0.63
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3ccccc3F)ccc2N)c1N1CCC[C@@H](N)C1
InChIKey: QVLHMFIFIGHQBW-CYBMUJFWSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 2.49 nM (pChEMBL 8.600000381469727)
Descriptors: MW 409.47, ALogP 2.38, HBA 7, HBD 3, PSA 115.09, QED 0.61
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1N1CCCC(N)CC1
InChIKey: JEVIKKKBDOXJFA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.022 nM (pChEMBL 10.65999984741211)
Descriptors: MW 447.52, ALogP 2.97, HBA 8, HBD 3, PSA 115.09, QED 0.57
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3ccccc3F)ccc2N)c1N1CCCC(N)CC1
InChIKey: MZEDYGZPEWMQOQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.115 nM (pChEMBL 9.9399995803833)
Descriptors: MW 423.5, ALogP 2.77, HBA 7, HBD 3, PSA 115.09, QED 0.59
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1OCC1CCNCC1
InChIKey: RMTGQRSHUXJNTH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 1.14 nM (pChEMBL 8.9399995803833)
Descriptors: MW 448.5, ALogP 3.03, HBA 8, HBD 3, PSA 107.09, QED 0.54
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3ccccc3F)ccc2N)c1OC1CCNCC1
InChIKey: MVCMGBIAYBTDLE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 4.97 nM (pChEMBL 8.300000190734863)
Descriptors: MW 410.45, ALogP 2.59, HBA 7, HBD 3, PSA 107.09, QED 0.6
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3ccccc3F)cnc2N)c1N1CCC[C@H](N)C1
InChIKey: DYXVMMFGWUCEJQ-LBPRGKRZSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 2.13 nM (pChEMBL 8.670000076293945)
Descriptors: MW 410.46, ALogP 1.78, HBA 8, HBD 3, PSA 127.98, QED 0.6
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1OC1CCNCC1
InChIKey: ZZPSHDYFXGODPI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 434.47, ALogP 2.79, HBA 8, HBD 3, PSA 107.09, QED 0.57
Compound (SMILES): Cn1ncc(NC(=O)c2nc(Br)cnc2N)c1N1CCC[C@H](N)C1
InChIKey: OEJMEIAMVNPZBT-QMMMGPOBSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 38.8 nM (pChEMBL 7.409999847412109)
Descriptors: MW 395.27, ALogP 0.73, HBA 8, HBD 3, PSA 127.98, QED 0.7
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3ccccc3F)cnc2N)c1N1CCC(N)CC1
InChIKey: NHGHGBJFWZDMBT-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.962 nM (pChEMBL 9.020000457763672)
Descriptors: MW 410.46, ALogP 1.78, HBA 8, HBD 3, PSA 127.98, QED 0.6
Compound (SMILES): Cn1ncc(NC(=O)c2nc(Cl)cnc2N)c1N1CCC[C@H](N)C1
InChIKey: UAPQZSZCXXFKCX-QMMMGPOBSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 137 nM (pChEMBL 6.860000133514404)
Descriptors: MW 350.81, ALogP 0.63, HBA 8, HBD 3, PSA 127.98, QED 0.74
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3ccccc3F)ccc2N)c1N1CC[C@@H](N)C1
InChIKey: LNIXAFUYUNLOOW-GFCCVEGCSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 1.92 nM (pChEMBL 8.720000267028809)
Descriptors: MW 395.44, ALogP 1.99, HBA 7, HBD 3, PSA 115.09, QED 0.62
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3ccccc3F)ccc2N)c1N1CCC[C@H](CN)C1
InChIKey: VJXUXTWQBIILQL-CQSZACIVSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.343 nM (pChEMBL 9.460000038146973)
Descriptors: MW 423.5, ALogP 2.63, HBA 7, HBD 3, PSA 115.09, QED 0.58
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1N1CC[C@H](CN)C1
InChIKey: AUSOZFFBBXRILI-SNVBAGLBSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.344 nM (pChEMBL 9.460000038146973)
Descriptors: MW 433.49, ALogP 2.44, HBA 8, HBD 3, PSA 115.09, QED 0.57
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1N1CCC[C@@H](N)CC1
InChIKey: JEVIKKKBDOXJFA-LLVKDONJSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.167 nM (pChEMBL 9.779999732971191)
Descriptors: MW 447.52, ALogP 2.97, HBA 8, HBD 3, PSA 115.09, QED 0.57
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3ccccc3F)ccc2N)c1N1CCC[C@H](N)CC1
InChIKey: MZEDYGZPEWMQOQ-AWEZNQCLSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 3.13 nM (pChEMBL 8.5)
Descriptors: MW 423.5, ALogP 2.77, HBA 7, HBD 3, PSA 115.09, QED 0.59
Compound (SMILES): Cn1ncc(NC(=O)c2cncc(-c3ccccc3F)n2)c1N1CCC[C@H](N)CC1
InChIKey: YVTVCGFWYNABGD-AWEZNQCLSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 581 nM (pChEMBL 6.239999771118164)
Descriptors: MW 409.47, ALogP 2.59, HBA 7, HBD 2, PSA 101.96, QED 0.69
Compound (SMILES): CN1CCC(c2c(NC(=O)c3nc(-c4c(F)cccc4F)sc3N)cnn2C)CC1
InChIKey: UWKVKWLSOMBHTE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 7.65 nM (pChEMBL 8.119999885559082)
Descriptors: MW 432.5, ALogP 3.47, HBA 7, HBD 2, PSA 89.07, QED 0.66
Compound (SMILES): Cn1ncc(NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)c1N1CCC[C@@H](N)CC1
InChIKey: LCLHYQYLXQMIBR-CYBMUJFWSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 2.48 nM (pChEMBL 8.609999656677246)
Descriptors: MW 444.46, ALogP 3.47, HBA 6, HBD 2, PSA 89.07, QED 0.64
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1C1CCNCC1
InChIKey: LLQIYQUPTCRRAL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 6.12 nM (pChEMBL 8.210000038146973)
Descriptors: MW 418.47, ALogP 3.12, HBA 7, HBD 3, PSA 97.86, QED 0.6
Compound (SMILES): CN[C@H]1CCCN(c2c(NC(=O)c3nc(-c4c(F)cccc4F)sc3N)cnn2C)CC1
InChIKey: OUBKTSCIYLAKMV-LBPRGKRZSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.096 nM (pChEMBL 10.020000457763672)
Descriptors: MW 461.54, ALogP 3.23, HBA 8, HBD 3, PSA 101.1, QED 0.54
Compound (SMILES): Nc1sc(-c2c(F)cccc2F)nc1C(=O)Nc1cnn(CCF)c1
InChIKey: XCFKWUCNYGYTAY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 11.9 nM (pChEMBL 7.920000076293945)
Descriptors: MW 367.36, ALogP 3.09, HBA 6, HBD 2, PSA 85.83, QED 0.73
Compound (SMILES): CCn1ncc(NC(=O)c2nc(-c3ccccc3F)sc2N)c1N1CCC[C@@H](N)CC1
InChIKey: DZPWHGFOCWIUKE-CYBMUJFWSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 443.55, ALogP 3.32, HBA 8, HBD 3, PSA 115.09, QED 0.56
Compound (SMILES): Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1C1CCC(N)CC1
InChIKey: ZGTXKDRQZHGJAA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.
Measurement: Ki = 0.735 nM (pChEMBL 9.130000114440918)
Descriptors: MW 432.5, ALogP 3.64, HBA 7, HBD 3, PSA 111.85, QED 0.58
Compound (SMILES): CC1=NN=C(c2cc3c(C(F)(F)F)cccc3s2)c2cc3oc(=O)[nH]c3cc2C1
InChIKey: CQMLETFIENAKAA-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14867
Assay: Antagonist activity at human GABA-A alpha1 receptor expressed in HEK293 cell membranes assessed as inhibition of GABA-induced response preincubated for 40 mins followed by GABA addition by FLIPR assay
Measurement: IC50 = 479 nM (pChEMBL 6.320000171661377)
Descriptors: MW 415.4, ALogP 5.12, HBA 5, HBD 1, PSA 70.72, QED 0.47
Compound (SMILES): COc1ccc(F)cc1-c1nc2c(n1C(C)C)C(c1ccc(Cl)cc1C)N(c1cc(Cl)ccc1C)C2=O
InChIKey: ORAZTVIFLIRSQY-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of Cy5-labeled p53 derived TFSDLWKLL peptide binding to C-terminal biotin-labelled human MDM2 (2 to 188 residues) by TR-FRET assay
Measurement: IC50 = 0.14 nM (pChEMBL 9.850000381469727)
Descriptors: MW 538.45, ALogP 7.95, HBA 4, HBD 0, PSA 47.36, QED 0.26
Compound (SMILES): COc1ncc(-c2nc3c(n2C(C)C)C(c2ccc(Cl)cc2C)N(c2cc(Cl)ccc2C)C3=O)c(OC)n1
InChIKey: XBJHBEQDHSREQB-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of Cy5-labeled p53 derived TFSDLWKLL peptide binding to C-terminal biotin-labelled human MDM2 (2 to 188 residues) by TR-FRET assay
Measurement: IC50 = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 552.46, ALogP 6.61, HBA 7, HBD 0, PSA 82.37, QED 0.27
Compound (SMILES): COc1ccccc1-c1nc2c(n1C(C)C)C(c1ccc(Cl)cc1C)N(c1cccc(Cl)c1F)C2=O
InChIKey: KWTIXCAYTLZJLJ-UHFFFAOYSA-N
Target: Protein Mdm4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15151
Assay: Inhibition of p53 derived Cy5-TFSDLWKLL peptide binding to human MDMX (2 to 185 residues) by TR-FRET assay
Measurement: IC50 = 27800 nM (pChEMBL 4.559999942779541)
Descriptors: MW 524.42, ALogP 7.64, HBA 4, HBD 0, PSA 47.36, QED 0.27
Compound (SMILES): COc1ncc(-c2nc3c(n2C(C)C)[C@H](c2ccc(Cl)cc2)N(c2cc(Cl)cn(C)c2=O)C3=O)c(OC)n1
InChIKey: AGBSXNCBIWWLHD-FQEVSTJZSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Time Resolved Fluorescence Energy Transfer (TR-FRET) Assay: The inhibition of p53-MDM2 and p53-MDM4 interactions is measured by time resolved fluorescence energy transfer (TR-FRET). Fluorescence energy transfer (or Foerster resonance energy transfer) describes an energy transfer between donor and acceptor fluorescent molecules. For this assay, human MDM2 protein (amino acids 2-188) and human MDM4 protein (amino acids 2-185), tagged with a C-terminal biotin moiety, are used in combination with a Europium labeled streptavidin (Perkin Elmer, Inc., Waltham, Mass., USA) serving as the donor fluorophore. The p53 derived, Cy5 labeled peptide Cy5-TFSDLWKLL (p53 aa18-26) is the energy acceptor. Upon excitation of the donor molecule at 340 nm, binding interaction between MDM2 or MDM4 and the p53 peptide induces energy transfer and enhanced response at the acceptor emission wavelength at 665 nm.
Measurement: IC50 = 0.23 nM (pChEMBL 9.640000343322754)
Descriptors: MW 555.42, ALogP 4.69, HBA 9, HBD 0, PSA 104.37, QED 0.34
Compound (SMILES): C[C@@]1(c2cccc(NC(=O)c3ccc(Br)cn3)c2)COCC(N)=N1
InChIKey: HALWMQVNBCAXRZ-KRWDZBQOSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human cathepsin D using Mca-GKPILFFRLK(DNP)D-R-NH2 as a substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 389.25, ALogP 2.7, HBA 5, HBD 2, PSA 89.6, QED 0.84
Compound (SMILES): NC1=N[C@](CF)(c2cccc(NC(=O)c3ccc(Br)cn3)c2)COC1
InChIKey: GWTUALKYCOKUGL-KRWDZBQOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin) expressed in CHO cells co-expressing human APP751 assessed as decrease in amyloid beta 40 levels after 24 hrs by MSD electrochemiluminescence assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 407.24, ALogP 2.65, HBA 5, HBD 2, PSA 89.6, QED 0.82
Compound (SMILES): CC1(c2cc(NC(=O)c3ccc(Br)cn3)ccc2F)COCC(N)=N1
InChIKey: AWWAZUFXKKZKCD-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of wild type human APP751 expressed in CHO cells incubated for 24 hrs by immunoassay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 407.24, ALogP 2.84, HBA 5, HBD 2, PSA 89.6, QED 0.82
Compound (SMILES): C[C@@]1(c2cccc(NC(=O)c3ccc(Br)cn3)c2)CO[C@@](C)(C(F)(F)F)C(N)=N1
InChIKey: YGNDEESWZOXXLA-ZWKOTPCHSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human cathepsin D using Mca-GKPILFFRLK(DNP)D-R-NH2 as a substrate
Measurement: IC50 = 73000 nM (pChEMBL 4.139999866485596)
Descriptors: MW 471.28, ALogP 4.02, HBA 5, HBD 2, PSA 89.6, QED 0.71
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(Br)cn3)ccc2F)CO[C@@](C)(C(F)(F)F)C(N)=N1
InChIKey: XXUKTXRJOFQHLP-ZWKOTPCHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated 10 mins in presence of NADPH by solid phase extraction mass spectrometry analysis
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 489.27, ALogP 4.16, HBA 5, HBD 2, PSA 89.6, QED 0.63
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ncc(C#N)cn3)ccc2F)CO[C@@](C)(C(F)(F)F)C(N)=N1
InChIKey: KSZDQDUDHWUQCJ-ZWKOTPCHSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using bufuralol as substrate incubated 10 mins in presence of NADPH by solid phase extraction mass spectrometry analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 436.37, ALogP 2.66, HBA 7, HBD 2, PSA 126.28, QED 0.71
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ncc(Br)cn3)ccc2F)CO[C@@](C)(C(F)(F)F)C(N)=N1
InChIKey: MONBOQDZSLNZSN-DLBZAZTESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated 10 mins in presence of NADPH by solid phase extraction mass spectrometry analysis
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 490.26, ALogP 3.55, HBA 6, HBD 2, PSA 102.49, QED 0.64
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)CO[C@@](C)(C(F)(F)F)C(N)=N1
InChIKey: TWKUHRBKUHLJDI-RBUKOAKNSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of human recombinant BACE2 catalytic domain using FRET substrate
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 435.38, ALogP 3.27, HBA 6, HBD 2, PSA 113.39, QED 0.72
Compound (SMILES): Cc1cc(C#N)cnc1C(=O)Nc1ccc(F)c([C@]2(C(F)F)COCC(N)=N2)c1
InChIKey: DHIZXRDJXNCTKQ-IBGZPJMESA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human recombinant BACE1 catalytic domain in presence of FRET substrate
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 403.36, ALogP 2.5, HBA 6, HBD 2, PSA 113.39, QED 0.81
Compound (SMILES): CC1=NC2(CCOc3ccc(-c4cc(Cl)cc(Cl)c4)cc32)N=C1N
InChIKey: BTQYJGMMVLMRIM-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: TR-FRET Assay: The beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 ul) was then added, mixed.
Measurement: IC50 = 157 nM (pChEMBL 6.800000190734863)
Descriptors: MW 360.24, ALogP 4.43, HBA 4, HBD 1, PSA 59.97, QED 0.82
Compound (SMILES): CC1=NC2(CCOc3ccc(-c4cncc(Cl)c4)cc32)N=C1N
InChIKey: XNFNZERRRUIVBJ-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: sAPPbeta Release Assay: SH-SY5Y cells were cultured in DMEM/F-12 with Glutamax, 10% FCS and 1% non-essential amino acids and cryopreserved and stored at −140° C. at a concentration of 7.5-9.5×106 cells per vial. Thaw cells and seed at a conc. of around 10000 cells/well in DMEM/F-12 with Glutamax, 10% FCS and 1% non-essential amino acids to a 384-well tissue culture treated plate, 100 μL cell susp/well. The cell plates were then incubated for 7-24 h at 37° C., 5% CO2. The cell medium was removed, followed by addition of 30 μL compound diluted in DMEM/F-12 with Glutamax, 10% FCS, 1% non-essential amino acids and 1% PeSt to a final conc. of 1% DMSO. The compounds were incubated with the cells for 17 h (overnight) at 37° C., 5% CO2. Meso Scale Discovery (MSD) plates were used for the detection of sAPPβ release. MSD sAPPβ plates were blocked in 1% BSA in Tris wash buffer (40 μL/well) for 1 h on shake at r.t. and washed 1 time in Tris wash buffer (40 μL/well). 20 μL of medium was transferred to the pre-blocked and washed MSD sAPPβ microplates, and the cell plates were further used in an ATP assay to measure cytotoxicity. The MSD plates were incubated with shaking at r.t. for 2 h and the media discarded. 10 μL detection antibody was added (1 nM) per well followed by incubation with shaking at r.t. for 2 h and then discarded. 40 μL Read Buffer was added per well and the plates were read in a SECTOR Imager.
Measurement: IC50 = 941 nM (pChEMBL 6.03000020980835)
Descriptors: MW 326.79, ALogP 3.17, HBA 5, HBD 1, PSA 72.86, QED 0.87
Compound (SMILES): CC1=NC2(CCOc3ccc(-c4cc(F)cc(F)c4)cc32)N=C1N
InChIKey: XPBCXYLXDCQPPG-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: sAPPbeta Release Assay: SH-SY5Y cells were cultured in DMEM/F-12 with Glutamax, 10% FCS and 1% non-essential amino acids and cryopreserved and stored at −140° C. at a concentration of 7.5-9.5×106 cells per vial. Thaw cells and seed at a conc. of around 10000 cells/well in DMEM/F-12 with Glutamax, 10% FCS and 1% non-essential amino acids to a 384-well tissue culture treated plate, 100 μL cell susp/well. The cell plates were then incubated for 7-24 h at 37° C., 5% CO2. The cell medium was removed, followed by addition of 30 μL compound diluted in DMEM/F-12 with Glutamax, 10% FCS, 1% non-essential amino acids and 1% PeSt to a final conc. of 1% DMSO. The compounds were incubated with the cells for 17 h (overnight) at 37° C., 5% CO2. Meso Scale Discovery (MSD) plates were used for the detection of sAPPβ release. MSD sAPPβ plates were blocked in 1% BSA in Tris wash buffer (40 μL/well) for 1 h on shake at r.t. and washed 1 time in Tris wash buffer (40 μL/well). 20 μL of medium was transferred to the pre-blocked and washed MSD sAPPβ microplates, and the cell plates were further used in an ATP assay to measure cytotoxicity. The MSD plates were incubated with shaking at r.t. for 2 h and the media discarded. 10 μL detection antibody was added (1 nM) per well followed by incubation with shaking at r.t. for 2 h and then discarded. 40 μL Read Buffer was added per well and the plates were read in a SECTOR Imager.
Measurement: IC50 = 2880 nM (pChEMBL 5.539999961853027)
Descriptors: MW 327.33, ALogP 3.4, HBA 4, HBD 1, PSA 59.97, QED 0.87