PDB 3TTJ deposited: 2011-09-14 modified: 2012-02-08
Title Crystal Structure of JNK3 complexed with CC-359, a JNK inhibitor for the prevention of ischemia-reperfusion injury
Authors Albers, R., Ayala, L., Bahmanyar, S., Benish, B., Bennett, B., Bhagwat, S., Blease, K., Cathers, B.E., Celeridad, M., Chamberlain, P., Clareen, S.S., Cole, A.G., Delgado, M., Fan, R., Ghosh, S., Giegel, D., Henderson, I., Hilgraf, R., Hughes, K., Katz, J., Khatsenko, O., Kois, A., Krenitsky, V.P., Moghaddam, M., Muir, J., Nadolny, L., Nowakowski, J., Omholt, P., Pai, S., Raymon, H., Sahasrabudhe, K., Satoh, Y., Shirley, M.A., Sudbeck, E., Tang, Y., Wright, J., Xu, L.
Structure factors resolution 2.1 rfactor 0.20205 rfree 0.27234
DPI 0.56 theoretical min: 0.25

In this Letter we describe the optimization of an aminopurine lead (1) with modest potency and poor overall kinase selectivity which led to the identification of a series of potent, selective JNK inhibitors. Improvement in kinase selectivity was enabled by introduction of an aliphatic side chain at the C-2 position. CC-359 (2) was selected as a potential clinical candidate for diseases manifested by ischemia reperfusion injury.

Bioorg.Med.Chem.Lett. 2012 Feb; 22(3):1427-1432 doi:10.1016/j.bmcl.2011.12.028

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1944604
PubMed 22226655 BMCLE8
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3TTJ/0 3TTJ 0 monomer 0 1 1 2610