Summary
PDB 2O2U deposited: 2006-11-30 modified: 2011-07-13
Title Crystal structure of human JNK3 complexed with N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)-2-fluorobenzamide
Authors Angell, R.M., Atkinson, F.L., Brown, M.J., Christopher, J.A., Chuang, T.T., 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.
Method X-RAY DIFFRACTION
Structure factors resolution 2.45 rfactor 0.232 rfree 0.281
DPI 0.79 theoretical min: 0.37
Related PDB Entries 2O0U
Citations

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.

Bioorg.Med.Chem.Lett. 2007 Mar; 17(5):1296-1301 doi:10.1016/j.bmcl.2006.12.003

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1148840
PubMed 17194588 BMCLE8
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
2O2U/0 2O2U 0 monomer 0 1 1 2408