2o2u: Difference between revisions
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|PDB= 2o2u |SIZE=350|CAPTION= <scene name='initialview01'>2o2u</scene>, resolution 2.450Å | |PDB= 2o2u |SIZE=350|CAPTION= <scene name='initialview01'>2o2u</scene>, resolution 2.450Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=738:N-(3- | |LIGAND= <scene name='pdbligand=738:N-(3-CYANO-4,5,6,7-TETRAHYDRO-1-BENZOTHIEN-2-YL)-2-FLUOROBENZAMIDE'>738</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span> | ||
|GENE= MAPK10, JNK3, JNK3A, PRKM10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= MAPK10, JNK3, JNK3A, PRKM10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2o0u|2O0U]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2o2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o2u OCA], [http://www.ebi.ac.uk/pdbsum/2o2u PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2o2u RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
The identification and exploration of a novel, potent and selective series of N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of JNK2 and JNK3 kinases is described. Compounds 5a and 11a were identified as potent inhibitors of JNK3 (pIC50 6.7 and 6.6, respectively), with essentially equal potency against JNK2 (pIC50 6.5). Selectivity within the mitogen-activated protein kinase (MAPK) family, against JNK1, p38alpha and ERK2, was observed for the series. X-ray crystallography of 5e and 8a in JNK3 revealed a unique binding mode, with the 3-cyano substituent forming an H-bond acceptor interaction with the hinge region of the ATP-binding site. | The identification and exploration of a novel, potent and selective series of N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of JNK2 and JNK3 kinases is described. Compounds 5a and 11a were identified as potent inhibitors of JNK3 (pIC50 6.7 and 6.6, respectively), with essentially equal potency against JNK2 (pIC50 6.5). Selectivity within the mitogen-activated protein kinase (MAPK) family, against JNK1, p38alpha and ERK2, was observed for the series. X-ray crystallography of 5e and 8a in JNK3 revealed a unique binding mode, with the 3-cyano substituent forming an H-bond acceptor interaction with the hinge region of the ATP-binding site. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Rowland, P.]] | [[Category: Rowland, P.]] | ||
[[Category: Somers, D.]] | [[Category: Somers, D.]] | ||
[[Category: kinase]] | [[Category: kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:11:54 2008'' | ||
