lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC[C@@H](Nc1ccc(C)c(CN(C)CCC(=O)O)c1)c1cc(C)c(Cl)c(C)c1
InChIKey: MBPDMEVLUBJDGF-OAQYLSRUSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Receptor Calcium FLIPR Antagonist Assay: The assay measures intracellular changes of Ca2+ mediated by the synthetic probing agonist 3-{[2-(2-Trifluoromethyl-biphenyl-4-yl)-benzo[b]thiophen-5-ylmethyl]-amino}-propionic acid (GNF-AC-1) in the HeLa-S1P1/Galpha16 cell clone 1: HeLa (human cervix carcinoma, ATCC CCL2) cells stably expressing N-terminally myc-tagged human S1P1 receptors (GenBank accession No. NM001400; UNIPROT P21453) and promiscuous Galpha16 protein (GenBank accession number M63904, Swissprot P30679) are cultured at 37 C., 5% CO2, and 95% relative humidity. The cells are plated in 384 well black plates (10'000 cells per well). After 24 hours the cells are loaded with Fluo-4-AM (1.6 uM in HBSS and 2.5 mM probenicid) for 1 hour at 37 C. After washing, the cells are transferred to the FLIPR. The test compounds are added at different concentrations (<=100 uM) in HBSS in the presence of 0.1% BSA and changes in fluorescence are recorded (indication of agonism).
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 402.97, ALogP 5.73, HBA 3, HBD 2, PSA 52.57, QED 0.56
Compound (SMILES): Cc1cc([C@H](Nc2ccc(C)c(CN3CCC(C)(C(=O)O)C3)c2)C(F)(F)F)ccc1Cl
InChIKey: ITWPTRRHRUZION-AIBWNMTMSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Receptor Calcium FLIPR Antagonist Assay: The assay measures intracellular changes of Ca2+ mediated by the synthetic probing agonist 3-{[2-(2-Trifluoromethyl-biphenyl-4-yl)-benzo[b]thiophen-5-ylmethyl]-amino}-propionic acid (GNF-AC-1) in the HeLa-S1P1/Galpha16 cell clone 1: HeLa (human cervix carcinoma, ATCC CCL2) cells stably expressing N-terminally myc-tagged human S1P1 receptors (GenBank accession No. NM001400; UNIPROT P21453) and promiscuous Galpha16 protein (GenBank accession number M63904, Swissprot P30679) are cultured at 37 C., 5% CO2, and 95% relative humidity. The cells are plated in 384 well black plates (10'000 cells per well). After 24 hours the cells are loaded with Fluo-4-AM (1.6 uM in HBSS and 2.5 mM probenicid) for 1 hour at 37 C. After washing, the cells are transferred to the FLIPR. The test compounds are added at different concentrations (<=100 uM) in HBSS in the presence of 0.1% BSA and changes in fluorescence are recorded (indication of agonism).
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 454.92, ALogP 5.97, HBA 3, HBD 2, PSA 52.57, QED 0.56
Compound (SMILES): Cc1cc([C@H](Nc2cc(CN3CC[C@@H](C(=O)O)C3)c(Cl)cn2)C(F)(F)F)ccc1Cl
InChIKey: QNSKFSYNLGLARS-ACJLOTCBSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Receptor Calcium FLIPR Antagonist Assay: The assay measures intracellular changes of Ca2+ mediated by the synthetic probing agonist 3-{[2-(2-Trifluoromethyl-biphenyl-4-yl)-benzo[b]thiophen-5-ylmethyl]-amino}-propionic acid (GNF-AC-1) in the HeLa-S1P1/Galpha16 cell clone 1: HeLa (human cervix carcinoma, ATCC CCL2) cells stably expressing N-terminally myc-tagged human S1P1 receptors (GenBank accession No. NM001400; UNIPROT P21453) and promiscuous Galpha16 protein (GenBank accession number M63904, Swissprot P30679) are cultured at 37 C., 5% CO2, and 95% relative humidity. The cells are plated in 384 well black plates (10'000 cells per well). After 24 hours the cells are loaded with Fluo-4-AM (1.6 uM in HBSS and 2.5 mM probenicid) for 1 hour at 37 C. After washing, the cells are transferred to the FLIPR. The test compounds are added at different concentrations (<=100 uM) in HBSS in the presence of 0.1% BSA and changes in fluorescence are recorded (indication of agonism).
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 462.3, ALogP 5.32, HBA 4, HBD 2, PSA 65.46, QED 0.61
Compound (SMILES): Cc1cc([C@H](Nc2cc(CNCCC(=O)O)c(Cl)cn2)C(F)(F)F)ccc1Cl
InChIKey: FXDMHLGLBQXSMG-KRWDZBQOSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Receptor Calcium FLIPR Antagonist Assay: The assay measures intracellular changes of Ca2+ mediated by the synthetic probing agonist 3-{[2-(2-Trifluoromethyl-biphenyl-4-yl)-benzo[b]thiophen-5-ylmethyl]-amino}-propionic acid (GNF-AC-1) in the HeLa-S1P1/Galpha16 cell clone 1: HeLa (human cervix carcinoma, ATCC CCL2) cells stably expressing N-terminally myc-tagged human S1P1 receptors (GenBank accession No. NM001400; UNIPROT P21453) and promiscuous Galpha16 protein (GenBank accession number M63904, Swissprot P30679) are cultured at 37 C., 5% CO2, and 95% relative humidity. The cells are plated in 384 well black plates (10'000 cells per well). After 24 hours the cells are loaded with Fluo-4-AM (1.6 uM in HBSS and 2.5 mM probenicid) for 1 hour at 37 C. After washing, the cells are transferred to the FLIPR. The test compounds are added at different concentrations (<=100 uM) in HBSS in the presence of 0.1% BSA and changes in fluorescence are recorded (indication of agonism).
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 436.26, ALogP 4.98, HBA 4, HBD 3, PSA 74.25, QED 0.51
Compound (SMILES): CCn1cc(-c2cnc3ccc(NC(=O)NCCCCc4ccccc4)nc3n2)cn1
InChIKey: GOJYPSLJBMWWEP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 415.5, ALogP 4.05, HBA 6, HBD 2, PSA 97.62, QED 0.42
Compound (SMILES): O=C(NCCCCc1ccccc1)Nc1ccc2ncc(-c3cnn(CCN4CCOCC4)c3)nc2n1
InChIKey: JCXBSFZMBCBDAC-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 500.61, ALogP 3.36, HBA 8, HBD 2, PSA 110.09, QED 0.32
Compound (SMILES): Cn1cc(-c2cnc3ccc(NC(=O)NCCCCc4ccccc4)nc3n2)cn1
InChIKey: HRZFVUBUANHQSK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 401.47, ALogP 3.57, HBA 6, HBD 2, PSA 97.62, QED 0.46
Compound (SMILES): COc1cc(CO)ccc1-c1cnc2ccc(NC(=O)N[C@H](C)CCCc3ccccc3)nc2n1
InChIKey: WOXOUQHZPMBXSJ-GOSISDBHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 471.56, ALogP 4.73, HBA 6, HBD 3, PSA 109.26, QED 0.33
Compound (SMILES): C[C@H](CCCc1ccccc1)NC(=O)Nc1ccc2ncc(-c3ccncc3)nc2n1
InChIKey: BQJCIWPXUFAVBN-QGZVFWFLSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 412.5, ALogP 4.62, HBA 5, HBD 2, PSA 92.69, QED 0.46
Compound (SMILES): COc1c(CO)cccc1-c1cnc2ccc(NC(=O)N[C@H](C)CCCc3ccccc3)nc2n1
InChIKey: RDVDGQUJOQXOGN-GOSISDBHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 471.56, ALogP 4.73, HBA 6, HBD 3, PSA 109.26, QED 0.33
Compound (SMILES): O=C(NCCCCc1ccccc1)Nc1ccc2ncc(-c3cn[nH]c3)nc2n1
InChIKey: AEMAMUOMSOVQHW-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 387.45, ALogP 3.56, HBA 5, HBD 3, PSA 108.48, QED 0.42
Compound (SMILES): O=C(NCCCCc1ccccc1)Nc1ccc2ncc(-c3ccc(O)cc3)nc2n1
InChIKey: YEFICWLMKHAHHW-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 413.48, ALogP 4.54, HBA 5, HBD 3, PSA 100.03, QED 0.39
Compound (SMILES): COc1ncccc1-c1cnc2ccc(NC(=O)N[C@H](C)CCCc3ccccc3)nc2n1
InChIKey: ZOQQEQQVKRGAQP-QGZVFWFLSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 442.52, ALogP 4.63, HBA 6, HBD 2, PSA 101.92, QED 0.41
Compound (SMILES): O=C(NCCCCc1ccccc1)Nc1ccc2ncc(-c3cnn(CCCO)c3)nc2n1
InChIKey: FDHGWFCXSXEKNU-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 445.53, ALogP 3.42, HBA 7, HBD 3, PSA 117.85, QED 0.32
Compound (SMILES): O=C(NCCCCc1ccccc1)Nc1ccc2ncc(-c3cnn(CC(F)F)c3)nc2n1
InChIKey: SLFNZIYIXQVRDI-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 451.48, ALogP 4.3, HBA 6, HBD 2, PSA 97.62, QED 0.37
Compound (SMILES): CC(CCCc1ccccc1)NC(=O)Nc1ccc2ncc(-c3cnn(C)c3)nc2n1
InChIKey: XQLYKWRLTPXWLG-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 415.5, ALogP 3.96, HBA 6, HBD 2, PSA 97.62, QED 0.48
Compound (SMILES): O=C(NCCCCc1ccccc1)Nc1ccc2ncc(-c3ccc(OP(=O)(O)O)cc3)nc2n1
InChIKey: XXFXTHMBZIFDFH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 493.46, ALogP 4.31, HBA 6, HBD 4, PSA 146.56, QED 0.2
Compound (SMILES): C[C@H](CCCc1ccccc1)NC(=O)Nc1ccc2ncc(N3CCOCC3)nc2n1
InChIKey: HYQASUBKZNTTPN-QGZVFWFLSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 420.52, ALogP 3.39, HBA 6, HBD 2, PSA 92.27, QED 0.61
Compound (SMILES): C[C@H](CCCc1ccccc1)NC(=O)Nc1ccc2ncc(-c3ccc(CO)cc3)nc2n1
InChIKey: KTTLITJDKBYFRM-GOSISDBHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 441.54, ALogP 4.72, HBA 5, HBD 3, PSA 100.03, QED 0.37
Compound (SMILES): C[C@H](CCCc1ccccc1)NC(=O)Nc1ccc2ncc(-c3cnn(CCN4CCOCC4)c3)nc2n1
InChIKey: IURZCUCAJQJUQB-OAQYLSRUSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 514.63, ALogP 3.75, HBA 8, HBD 2, PSA 110.09, QED 0.33
Compound (SMILES): Cn1cc(-c2cnc3ccc(NC(=O)NCCCC(C)(C)c4ccccc4)nc3n2)cn1
InChIKey: UUTGYXYCCNOGAN-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 429.53, ALogP 4.3, HBA 6, HBD 2, PSA 97.62, QED 0.43
Compound (SMILES): CCCn1cc(-c2cnc3ccc(NC(=O)N[C@H](C)CCCc4ccccc4)nc3n2)cn1
InChIKey: MLZSHDLFCMASLV-GOSISDBHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 443.56, ALogP 4.83, HBA 6, HBD 2, PSA 97.62, QED 0.39
Compound (SMILES): C[C@H](CCCc1ccccc1)NC(=O)Nc1ccc2ncc(-c3cn[nH]c3)nc2n1
InChIKey: MRVGTQOGHZOPPZ-OAHLLOKOSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 401.47, ALogP 3.95, HBA 5, HBD 3, PSA 108.48, QED 0.43
Compound (SMILES): O=C(NCCCCc1ccccc1)Nc1ccc2ncc(N3CCCC3)nc2n1
InChIKey: ZZWRWYBPGWAMFH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 390.49, ALogP 3.77, HBA 5, HBD 2, PSA 83.04, QED 0.6
Compound (SMILES): C[C@H](CCCc1ccccc1)NC(=O)Nc1ccc2ncc(N3CCCC3)nc2n1
InChIKey: HNXFBBUXHDXTJA-QGZVFWFLSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 404.52, ALogP 4.16, HBA 5, HBD 2, PSA 83.04, QED 0.62
Compound (SMILES): O=C(NCCCCc1ccccc1)Nc1ccc2ncc(-c3ccc(O)c(F)c3)nc2n1
InChIKey: NGKJEYVOLSWDQJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 431.47, ALogP 4.68, HBA 5, HBD 3, PSA 100.03, QED 0.37
Compound (SMILES): O=C(NCCCCc1ccccc1)Nc1ccc2ncc(-c3cccc(CO)c3)nc2n1
InChIKey: FNRZJZHDLZAOOT-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 427.51, ALogP 4.33, HBA 5, HBD 3, PSA 100.03, QED 0.36
Compound (SMILES): O=C(NCCCCc1ccccc1)Nc1ccc2ncc(N3CCOCC3)nc2n1
InChIKey: WDZIFPGUPLYIOC-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 406.49, ALogP 3.01, HBA 6, HBD 2, PSA 92.27, QED 0.59
Compound (SMILES): Cc1n[nH]c(C)c1-c1cnc2ccc(NC(=O)N[C@H](C)CCCc3ccccc3)nc2n1
InChIKey: IIAJWBPEBWWBOO-OAHLLOKOSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 429.53, ALogP 4.56, HBA 5, HBD 3, PSA 108.48, QED 0.4
Compound (SMILES): COc1ccc(-c2cnc3ccc(NC(=O)NCCCCc4ccccc4)nc3n2)cc1OC
InChIKey: VLTWGPTYUIJLBH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 457.53, ALogP 4.85, HBA 6, HBD 2, PSA 98.26, QED 0.35
Compound (SMILES): COc1ccccc1-c1cnc2ccc(NC(=O)N[C@H](C)CCCc3ccccc3)nc2n1
InChIKey: JLUFJKSVQNRARA-GOSISDBHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 441.54, ALogP 5.23, HBA 5, HBD 2, PSA 89.03, QED 0.39
Compound (SMILES): C[C@H](CCCc1ccccc1)NC(=O)Nc1ccc2ncc(-c3cnn(C)c3)nc2n1
InChIKey: XQLYKWRLTPXWLG-MRXNPFEDSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 415.5, ALogP 3.96, HBA 6, HBD 2, PSA 97.62, QED 0.48
Compound (SMILES): C[C@H](CCCc1ccccc1)NC(=O)Nc1ccc2ncc(-c3cccc(CO)c3)nc2n1
InChIKey: CHAGWGHZPPNDNU-GOSISDBHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 441.54, ALogP 4.72, HBA 5, HBD 3, PSA 100.03, QED 0.37
Compound (SMILES): O=C(NCCCCc1ccccc1)Nc1ccc2ncc(-c3cnn(CCO)c3)nc2n1
InChIKey: CMXSJFRYXLKZDO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 431.5, ALogP 3.03, HBA 7, HBD 3, PSA 117.85, QED 0.35
Compound (SMILES): COc1cc(-c2cnc3ccc(NC(=O)NCCCCc4ccccc4)nc3n2)ccc1C(=O)O
InChIKey: HCOWABUPDFCPCU-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 471.52, ALogP 4.54, HBA 6, HBD 3, PSA 126.33, QED 0.31
Compound (SMILES): C[C@H](CCCc1ccccc1)NC(=O)Nc1ccc2ncc(-c3ccc(C[C@H](N)C(=O)O)cc3)nc2n1
InChIKey: GDOAISQRCKGMNI-GCJKJVERSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 498.59, ALogP 4.18, HBA 6, HBD 4, PSA 143.12, QED 0.26
Compound (SMILES): C[C@H](CCCc1ccccc1)NC(=O)Nc1ccc2ncc(-c3cccc(C(=O)O)c3)nc2n1
InChIKey: AFDKXUCGBCYLCU-QGZVFWFLSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 455.52, ALogP 4.92, HBA 5, HBD 3, PSA 117.1, QED 0.35
Compound (SMILES): N[C@@H](Cc1ccc(-c2cnc3ccc(NC(=O)NCCCCc4ccccc4)nc3n2)cc1)C(=O)O
InChIKey: RRPSJYRYDSYTQG-NRFANRHFSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assays: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). MAPK-ALPHAs (e.g. Erk2): the test substance, 0.625 ng Erk2 (#14-173, Upstate), 10 uM ATP and 15 nM biotinylated MBP (myelin basic protein) substrate were incubated on a 384-well Optiplate (Perkin-Elmer) in a volume of 15 ul for 1 h in 25 mM Tris, 10 mM MgCl2, 0.1% Tween-20, 100 uM NaVO4, 2 mM DTT at pH 7.5.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 484.56, ALogP 3.79, HBA 6, HBD 4, PSA 143.12, QED 0.25