2O0U

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

Summary for 2O0U

• Entry DOI: 10.2210/pdb2o0u/pdb
• Descriptor: Mitogen-activated protein kinase 10, N-{3-CYANO-6-[3-(1-PIPERIDINYL)PROPANOYL]-4,5,6,7-TETRAHYDROTHIENO[2,3-C]PYRIDIN-2-YL}1-NAPHTHALENECARBOXAMIDE (3 entities in total)
• Functional Keywords: kinase fold, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P53779
• Total number of polymer chains: 1
• Total formula weight: 42532.28

Authors

Rowland, P.,Somers, D. (deposition date: 2006-11-28, release date: 2007-02-27, Last modification date: 2023-12-27)

Primary citation

Angell, R.M.,Atkinson, F.L.,Brown, M.J.,Chuang, T.T.,Christopher, J.A.,Cichy-Knight, M.,Dunn, A.K.,Hightower, K.E.,Malkakorpi, S.,Musgrave, J.R.,Neu, M.,Rowland, P.,Shea, R.L.,Smith, J.L.,Somers, D.O.,Thomas, S.A.,Thompson, G.,Wang, R.
N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3.
Bioorg.Med.Chem.Lett., 17:1296-1301, 2007

PubMed Abstract: 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.

PubMed: 17194588
DOI: 10.1016/j.bmcl.2006.12.003

Experimental method

X-RAY DIFFRACTION (2.1 Å)