lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): [C-]#[N+]c1cnc2c(NC3CC3)nc(Nc3cc(C#N)cc(N4CCN(C5COC5)CC(F)C4)c3Cl)nn12
InChIKey: QZXOHCNHILBVDI-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.29 nM (pChEMBL 9.539999961853027)
Descriptors: MW 522.98, ALogP 3.38, HBA 10, HBD 2, PSA 111, QED 0.47
Compound (SMILES): [C-]#[N+]c1cnc2c(NC3CC3)nc(Nc3cc(C#N)cc(N4CCN(C5COC5)C(C(=O)N5CCOCC5)C4)c3Cl)nn12
InChIKey: MHFGVXATTJEHKF-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 1.32 nM (pChEMBL 8.880000114440918)
Descriptors: MW 604.08, ALogP 2.27, HBA 12, HBD 2, PSA 140.54, QED 0.38
Compound (SMILES): CC(=O)N1CC(N2CCC(c3cc(C#N)cc(Nc4nc(NC5CC5)c5ncc(C#N)n5n4)c3Cl)CC2)C1
InChIKey: DRQLCOQYWKMOBR-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.28 nM (pChEMBL 9.550000190734863)
Descriptors: MW 531.02, ALogP 3.25, HBA 10, HBD 2, PSA 138.27, QED 0.49
Compound (SMILES): [C-]#[N+]c1cnc2c(NCC)nc(Nc3cc(C#N)cc(N4CC[C@@H](NC(=O)OC)[C@H](O)C4)c3Cl)nn12
InChIKey: RKAFZEOLMPAXTF-CZUORRHYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 4.71 nM (pChEMBL 8.329999923706055)
Descriptors: MW 510.95, ALogP 2.67, HBA 11, HBD 4, PSA 157.09, QED 0.36
Compound (SMILES): [C-]#[N+]c1cnc2c(NCC)nc(Nc3cc(C#N)cc(N4CC[C@H](NC(=O)OC)[C@@H](O)C4)c3Cl)nn12
InChIKey: RKAFZEOLMPAXTF-BBRMVZONSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.13 nM (pChEMBL 9.890000343322754)
Descriptors: MW 510.95, ALogP 2.67, HBA 11, HBD 4, PSA 157.09, QED 0.36
Compound (SMILES): [C-]#[N+]c1cnc2c(NCC)nc(Nc3cc(C#N)cc(C4CCNCC4)c3Cl)nn12
InChIKey: AJQFWTSVDRWMDI-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.76 nM (pChEMBL 9.119999885559082)
Descriptors: MW 421.9, ALogP 3.84, HBA 8, HBD 3, PSA 107.32, QED 0.54
Compound (SMILES): CCNc1nc(Nc2cc(C#N)cc(N3CC[C@@H]4[C@@H](C3)OCCN4C3COC3)c2Cl)nn2c(C#N)cnc12
InChIKey: APRPPVBWMLGDJB-TZIWHRDSSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.52 nM (pChEMBL 9.279999732971191)
Descriptors: MW 535.01, ALogP 2.37, HBA 12, HBD 2, PSA 139.66, QED 0.48
Compound (SMILES): [C-]#[N+]c1cnc2c(NC3CC3)nc(Nc3cc(C#N)cc(N4CC(N5CCN(C)CC5)C4)c3F)nn12
InChIKey: CGRMVYHEYBWHEW-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.61 nM (pChEMBL 9.210000038146973)
Descriptors: MW 487.55, ALogP 2.44, HBA 10, HBD 2, PSA 105.01, QED 0.51
Compound (SMILES): [C-]#[N+]c1cnc2c(NCC)nc(Nc3cc(C(F)F)cc(N4CCN(C5COC5)CC4)c3Cl)nn12
InChIKey: VWKPZETYLPHTBG-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 503.95, ALogP 3.96, HBA 9, HBD 2, PSA 87.21, QED 0.47
Compound (SMILES): [C-]#[N+]c1cnc2c(Nc3nc(C)n(C)n3)nc(Nc3ccc4c(c3)c(C#N)nn4C)nn12
InChIKey: ZLXJMFINYROVQB-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.13 nM (pChEMBL 9.890000343322754)
Descriptors: MW 425.42, ALogP 2.36, HBA 12, HBD 2, PSA 143.82, QED 0.41
Compound (SMILES): [C-]#[N+]c1cnc2c(Nc3nc(C)n(C)n3)nc(Nc3ccc4c(c3)c(C#N)nn4C[C@@H](C)O)nn12
InChIKey: AXCZPENGSHNULO-LLVKDONJSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 7.54 nM (pChEMBL 8.119999885559082)
Descriptors: MW 469.47, ALogP 2.2, HBA 13, HBD 3, PSA 164.05, QED 0.31
Compound (SMILES): CCNc1nc(Nc2ccc3c(c2)c(C#N)nn3C2CCN(C[C@H](C)O)CC2)nn2c(C#N)cnc12
InChIKey: YAJPADUCIGBWGI-HNNXBMFYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.27 nM (pChEMBL 9.569999694824219)
Descriptors: MW 485.56, ALogP 2.41, HBA 12, HBD 3, PSA 156.01, QED 0.36
Compound (SMILES): CCNc1nc(Nc2ccc3c(c2)c(C#N)nn3C2CCN(C[C@@H](C)O)CC2)nn2c(C#N)cnc12
InChIKey: YAJPADUCIGBWGI-OAHLLOKOSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 485.56, ALogP 2.41, HBA 12, HBD 3, PSA 156.01, QED 0.36
Compound (SMILES): CCNc1nc(Nc2ccc3c(c2)c(C#N)nn3C2CCN(C3COC3)CC2)nn2c(C#N)cnc12
InChIKey: QOOUYJSMLUCYMO-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 1.44 nM (pChEMBL 8.84000015258789)
Descriptors: MW 483.54, ALogP 2.43, HBA 12, HBD 2, PSA 145.01, QED 0.42
Compound (SMILES): C=Cc1cc(C#N)cc(Nc2nc(NC3CC3)c3ncc(C#N)n3n2)c1Cl
InChIKey: FUXSYWZCKDTTKK-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 376.81, ALogP 3.48, HBA 8, HBD 2, PSA 114.72, QED 0.7
Compound (SMILES): N#Cc1cc(CO)c(Cl)c(Nc2nc(NC3CC3)c3ncc(C#N)n3n2)c1
InChIKey: FYSJARATYIAUQN-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.11 nM (pChEMBL 9.960000038146973)
Descriptors: MW 380.8, ALogP 2.33, HBA 9, HBD 3, PSA 134.95, QED 0.61
Compound (SMILES): CCNc1nc(Nc2cc(C#N)cc(N3CCN(C4COC4)CC3)c2Cl)nn2c(C#N)cnc12
InChIKey: HJGJLSSJJLDPPL-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.23 nM (pChEMBL 9.640000343322754)
Descriptors: MW 478.95, ALogP 2.22, HBA 11, HBD 2, PSA 130.43, QED 0.54
Compound (SMILES): N#Cc1cc(Nc2nc(NC3CC3)c3ncc(C#N)n3n2)c(Cl)c(NC2CCN(C3COC3)CC2)c1
InChIKey: DCAIOCXHNAGAPE-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 0.82 nM (pChEMBL 9.09000015258789)
Descriptors: MW 504.99, ALogP 3.11, HBA 11, HBD 3, PSA 139.22, QED 0.44
Compound (SMILES): CC1(C)CC(Oc2cc(F)c(Nc3nc(NC4CC4)c4ncc(C#N)n4n3)cc2C#N)CC(C)(C)N1
InChIKey: JFNYQAQBEVVXEF-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 16.04 nM (pChEMBL 7.789999961853027)
Descriptors: MW 489.56, ALogP 4.01, HBA 10, HBD 3, PSA 135.98, QED 0.47
Compound (SMILES): CN1C(C)(C)CC(Oc2cc(F)c(C#N)cc2Nc2nc(NC3CC3)c3ncc(C#N)n3n2)CC1(C)C
InChIKey: DTJSREINAZNJOU-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 1.43 nM (pChEMBL 8.850000381469727)
Descriptors: MW 503.59, ALogP 4.35, HBA 10, HBD 2, PSA 127.19, QED 0.5
Compound (SMILES): CN1C(C)(C)CC(Oc2cc(OC3CC(C)(C)N(C)C(C)(C)C3)c(Nc3nc(NC4CC4)c4ncc(C#N)n4n3)cc2C#N)CC1(C)C
InChIKey: KKIONILKFAMLTA-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 60.08 nM (pChEMBL 7.21999979019165)
Descriptors: MW 654.86, ALogP 6.25, HBA 12, HBD 2, PSA 139.66, QED 0.29
Compound (SMILES): N#Cc1cc(Nc2nc(NC3CC3)c3ncc(C#N)n3n2)c(OC2CCNCC2)cc1F
InChIKey: QFLKZHBSVBIOAB-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 2.75 nM (pChEMBL 8.5600004196167)
Descriptors: MW 433.45, ALogP 2.46, HBA 10, HBD 3, PSA 135.98, QED 0.54
Compound (SMILES): CCNc1nc(Nc2cc(C#N)cc(N3CCN(CC(F)F)CC3)c2Cl)nn2c(C#N)cnc12
InChIKey: KYFFLNPLWDNZLC-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 1.39 nM (pChEMBL 8.859999656677246)
Descriptors: MW 486.92, ALogP 3.08, HBA 10, HBD 2, PSA 121.2, QED 0.52
Compound (SMILES): [C-]#[N+]c1cnc2c(NC3CC3)nc(Nc3nc(C#N)ncc3Cl)nn12
InChIKey: BZQKBBAVVKXLHC-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates.
Measurement: IC50 = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 352.75, ALogP 2.31, HBA 9, HBD 2, PSA 121.07, QED 0.69
Compound (SMILES): C=CCN1CC(=O)N2[C@@H](Cc3ccc(O)cc3)C(=O)N(Cc3cccc4c(C(=O)Nc5ccc(N6CCCCC6)nc5)cn(C)c34)C[C@@H]2N1C(=O)NCc1ccccc1
InChIKey: NEQDCWFWVYOBKX-HHDOLNPSSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assay: This assay was performed in a 200 l volume in 96-well microtiter plates using cDNA-expressed human hepatic CYP3A4 (supersome, BD Gentest #456202). As a substrate for CYP3A4, 7-benzyloxy-4-trifluoromethyl-coumarin (BFC) was used. The compounds of Examples 1 to 5 and the substrate BFC were dissolved in 100% acetonitrile. The final volume of acetonitrile of the incubation mixture was less than 1% (volume/volume). A potassium phosphate buffer (pH 7.4, final concentration 0.1M), MgCl2 (final concentration 8.3 mM), EDTA (final concentration 1.67 mM), an inventive compound stock solution, CYP3A4 supersome, and NADPH (final concentration 0.25 mM) were added to each well. The reaction was initiated by adding the substrate (BFC, final concentration 30 M) at 37. The incubation was performed for 20 minutes and then the reaction was terminated by the addition of 75 ul of acetonitrile: 0.5 M tris-base=4:1 (volume/volume).Then, a fluorescent signal was measured using a fluorometer.
Measurement: IC50 = 12240 nM (pChEMBL 4.909999847412109)
Descriptors: MW 795.95, ALogP 5.26, HBA 9, HBD 3, PSA 146.59, QED 0.15
Compound (SMILES): Cc1ccccc1[C@H](C)NC(=O)c1ccc2c(c1)c(C)c(C)n2Cc1ccc(-c2ccccc2C(=O)O)cc1
InChIKey: HIZJHEWINJXBHY-QHCPKHFHSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of human PPARgamma in HEK293T cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 147 nM (pChEMBL 6.829999923706055)
Descriptors: MW 516.64, ALogP 7.47, HBA 3, HBD 2, PSA 71.33, QED 0.24
Compound (SMILES): CCOc1ccc([C@H](C)NC(=O)c2ccc3c(c2)c(C)c(C)n3Cc2ccc(-c3ccccc3C(=O)O)cc2)cc1
InChIKey: LTVKSFXRQPYAAJ-QHCPKHFHSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of human PPARgamma in HEK293T cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 546.67, ALogP 7.56, HBA 4, HBD 2, PSA 80.56, QED 0.2
Compound (SMILES): Cc1c(C)n(Cc2ccc(-c3ccccc3C(=O)O)cc2)c2ccc(C(=O)N[C@@H](C)c3ccccc3Br)cc12
InChIKey: AMSXUORYXQSRID-NRFANRHFSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of human PPARgamma in HEK293T cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 147 nM (pChEMBL 6.829999923706055)
Descriptors: MW 581.51, ALogP 7.93, HBA 3, HBD 2, PSA 71.33, QED 0.21
Compound (SMILES): CCc1ccccc1[C@H](C)NC(=O)c1ccc2c(c1)c(C)c(C)n2Cc1ccc(-c2ccccc2C(=O)O)cc1
InChIKey: ZWFGBYOUCRKLHM-QHCPKHFHSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of human PPARgamma in HEK293T cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 334 nM (pChEMBL 6.480000019073486)
Descriptors: MW 530.67, ALogP 7.73, HBA 3, HBD 2, PSA 71.33, QED 0.22
Compound (SMILES): Cc1c(C)n(Cc2ccc(-c3ccccc3C(=O)O)cc2)c2ccc(C(=O)N[C@@H](C)c3ccccc3OC(C)C)cc12
InChIKey: GUONGSVVVOLRQE-DEOSSOPVSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of human PPARgamma in HEK293T cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 4907 nM (pChEMBL 5.309999942779541)
Descriptors: MW 560.69, ALogP 7.95, HBA 4, HBD 2, PSA 80.56, QED 0.19
Compound (SMILES): Cc1c(C)n(Cc2ccc(-c3ccccc3C(=O)O)cc2)c2ccc(C(=O)N[C@@H](C)c3cccc(C4CC4)c3)cc12
InChIKey: WFYZRGARXVIIQQ-QHCPKHFHSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of human PPARgamma in HEK293T cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 4391 nM (pChEMBL 5.360000133514404)
Descriptors: MW 542.68, ALogP 8.04, HBA 3, HBD 2, PSA 71.33, QED 0.21
Compound (SMILES): Cc1c(C)n(Cc2ccc(-c3ccccc3C(=O)O)cc2)c2ccc(C(=O)NC3COc4ccccc4C3)cc12
InChIKey: XPCLROUCHIPBSJ-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Lanthascreen Competitive Binding Assay: The assay was performed according to manufacturer protocol. A mixture of nM GST-PPARG-LBD, 5 nM Tb-GST-antibody, 5 nM Fluormone Pan-PPAR Green, and serial dilutions of the experimental compound, beginning at 10 μM downwards, was added to wells of black 384-well low-volume plates (Greiner) to a total volume of 18 μL. All dilutions were made in TR-FRET assay buffer C. DMSO at 2% final concentration was used as a no-ligand control. Experiment was performed in triplicate, and incubated for 2 hours in the dark prior to assay read in Perkin Elmer ViewLux ultra HTS microplate reader. FRET signal was measured by excitation at 340 nm and emission at 520 nm for fluorescein and 490 nm for terbium. Fold change over DMSO was calculated using GraphPad Prism Software (La Jolla, Calif.) by calculating 520 nm/490 nm ratio. Graphs were plotted as fold change of FRET signal for compound treatment over DMSO-only control.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 530.62, ALogP 6.41, HBA 4, HBD 2, PSA 80.56, QED 0.27
Compound (SMILES): COc1cc(C2=C(c3cn(CCCOC(=O)C(N)CC(C)C)c4ccccc34)C(=O)NC2=O)cc(OC)c1OC
InChIKey: MHEYLSXQBQEYPZ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: The effect of test compounds on the activity of the protein kinases GSK-3β, VEGFR-2 and FLT-3 was evaluated based on half maximal inhibitory concentration (IC50) values determined by Millipore UK Ltd; Gemini Crescent; Dundee Technology Park; Dundee DD2 1SW; UK (IC50Profiler). Detailed protocols can be found at: www.millipore.com/drugdiscovery/dd3/assayprotocols.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 549.62, ALogP 3.54, HBA 9, HBD 2, PSA 131.11, QED 0.2
Compound (SMILES): COc1cc(C2=C(c3cn(CCOC(=O)C(N)CC(C)C)c4ccccc34)C(=O)NC2=O)cc(OC)c1OC
InChIKey: ZKLYZABPCRFWBD-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: The effect of test compounds on the activity of the protein kinases GSK-3β, VEGFR-2 and FLT-3 was evaluated based on half maximal inhibitory concentration (IC50) values determined by Millipore UK Ltd; Gemini Crescent; Dundee Technology Park; Dundee DD2 1SW; UK (IC50Profiler). Detailed protocols can be found at: www.millipore.com/drugdiscovery/dd3/assayprotocols.
Measurement: IC50 = 251 nM (pChEMBL 6.599999904632568)
Descriptors: MW 535.6, ALogP 3.15, HBA 9, HBD 2, PSA 131.11, QED 0.28
Compound (SMILES): COc1cc(C2=C(c3cn(CCCNC(=O)C(N)CC(C)C)c4ccccc34)C(=O)NC2=O)cc(OC)c1OC
InChIKey: JZBWCAHLSGAKDG-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: The effect of test compounds on the activity of the protein kinases GSK-3β, VEGFR-2 and FLT-3 was evaluated based on half maximal inhibitory concentration (IC50) values determined by Millipore UK Ltd; Gemini Crescent; Dundee Technology Park; Dundee DD2 1SW; UK (IC50Profiler). Detailed protocols can be found at: www.millipore.com/drugdiscovery/dd3/assayprotocols.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 548.64, ALogP 3.11, HBA 8, HBD 3, PSA 133.91, QED 0.23
Compound (SMILES): COc1cc(C2=C(c3cn(CCCO)c4ccccc34)C(=O)NC2=O)cc(OC)c1OC
InChIKey: IFUKBECSYNPLCY-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Kinase Assay: The effect of test compounds on the activity of the protein kinases GSK-3β, VEGFR-2 and FLT-3 was evaluated based on half maximal inhibitory concentration (IC50) values determined by Millipore UK Ltd; Gemini Crescent; Dundee Technology Park; Dundee DD2 1SW; UK (IC50Profiler). Detailed protocols can be found at: www.millipore.com/drugdiscovery/dd3/assayprotocols.
Measurement: IC50 = 3386 nM (pChEMBL 5.46999979019165)
Descriptors: MW 436.46, ALogP 2.62, HBA 7, HBD 2, PSA 99.02, QED 0.53
Compound (SMILES): N#C[C@H]1CCC[C@@H]1n1cc(C(N)=O)c(Nc2ccccc2)n1
InChIKey: QMBHRWPFACKJPC-RISCZKNCSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 mL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer #PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction.
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 295.35, ALogP 2.59, HBA 5, HBD 2, PSA 96.73, QED 0.91
Compound (SMILES): N#C[C@@H]1CCCCC1n1cc(C(N)=O)c(Nc2ccccc2)n1
InChIKey: DLZJFUWJIGTHDZ-SFVWDYPZSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 mL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer #PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction.
Measurement: IC50 = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 309.37, ALogP 2.98, HBA 5, HBD 2, PSA 96.73, QED 0.91
Compound (SMILES): CS(=O)(=O)c1ccc(Nc2nn([C@H]3CCC[C@@H]3C#N)cc2C(N)=O)cc1
InChIKey: OWOXRDCLWNAUFE-ABAIWWIYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 mL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer #PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction.
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 373.44, ALogP 1.99, HBA 7, HBD 2, PSA 130.87, QED 0.82
Compound (SMILES): CS(=O)(=O)c1ccc(Nc2nn([C@H]3CCC[C@H]3C#N)cc2C(N)=O)cc1
InChIKey: OWOXRDCLWNAUFE-NHYWBVRUSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 mL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer #PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 373.44, ALogP 1.99, HBA 7, HBD 2, PSA 130.87, QED 0.82
Compound (SMILES): [C-]#[N+][C@H]1CCCC[C@@H]1n1cc(C(N)=O)c(Nc2ccccc2)n1
InChIKey: PJKGHVBBXCIBQQ-GJZGRUSLSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 mL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer #PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction.
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 309.37, ALogP 3.13, HBA 4, HBD 2, PSA 77.3, QED 0.85
Compound (SMILES): N#C[C@H]1C[C@H](O)CCC1n1cc(C(N)=O)c(Nc2ccccc2)n1
InChIKey: ORNNCMDCJKDEKD-HNVBAWDGSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 mL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer #PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction.
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 325.37, ALogP 1.95, HBA 6, HBD 3, PSA 116.96, QED 0.79
Compound (SMILES): N#CC1CCC2(CC1n1cc(C(N)=O)c(Nc3ccccc3)n1)OCCO2
InChIKey: GOYVGGAPXFQVDR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 mL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer #PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 367.41, ALogP 2.33, HBA 7, HBD 2, PSA 115.19, QED 0.86
Compound (SMILES): COC(=O)C1CC[C@H](C#N)C(n2cc(C(N)=O)c(Nc3ccccc3)n2)C1
InChIKey: FKIICIGSBKQIRU-MFOWVQHXSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 mL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer #PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction.
Measurement: IC50 = 423 nM (pChEMBL 6.369999885559082)
Descriptors: MW 367.41, ALogP 2.38, HBA 7, HBD 2, PSA 123.03, QED 0.78