2o2u
From Proteopedia
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| , resolution 2.450Å | |||||||
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| Ligands: | |||||||
| Gene: | MAPK10, JNK3, JNK3A, PRKM10 (Homo sapiens) | ||||||
| Activity: | Mitogen-activated protein kinase, with EC number 2.7.11.24 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human JNK3 complexed with N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)-2-fluorobenzamide
Contents |
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.
Disease
Known diseases associated with this structure: Epileptic encephalopathy, Lennox-Gastaut type OMIM:[602897]
About this Structure
2O2U is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3., Angell RM, Atkinson FL, Brown MJ, Chuang TT, Christopher JA, Cichy-Knight M, Dunn AK, Hightower KE, Malkakorpi S, Musgrave JR, Neu M, Rowland P, Shea RL, Smith JL, Somers DO, Thomas SA, Thompson G, Wang R, Bioorg Med Chem Lett. 2007 Mar 1;17(5):1296-301. Epub 2006 Dec 15. PMID:17194588
Page seeded by OCA on Thu Mar 20 17:54:26 2008
