2o0u

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Revision as of 20:58, 12 November 2007

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spinqualitylabelsall models 2o0u, resolution 2.100Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of human JNK3 complexed with N-{3-cyano-6-[3-(1-piperidinyl)propanoyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl}-1-naphthalenecarboxamide

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 (pIC(50) 6.7 and 6.6, respectively), with, essentially equal potency against JNK2 (pIC(50) 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

2O0U is a Single protein structure of sequence from Homo sapiens with C0M as ligand. Active as Mitogen-activated protein kinase, with EC number 2.7.11.24 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

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