Summary
PDB 3TTI deposited: 2011-09-14 modified: 2012-02-08
Title Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor
Authors Albers, R., Ayala, L., Bahmanyar, S., Bai, A., Benish, B., Bennett, B., Blease, K., Bodine, T., Cathers, B.E., Celeridad, M., Chamberlain, P., Clareen, S.S., Delgado, M., Delker, S.L., D'Sidocky, N., Fan, R., Giegel, D., Hegde, S., Hilgraf, R., Katz, J., Khatsenko, O., Lachowitzer, J., McCarrick, M., Moghaddam, M., Muir, J., Nadolny, L., Plantevin Krenitsky, V., Raymon, H., Sapienza, J., Satoh, Y., Shirley, M.A., Tang, Y., Wright, J., Xu, L.
Method X-RAY DIFFRACTION
Structure factors resolution 2.2 rfactor 0.2418 rfree 0.3353
DPI 0.80 theoretical min: 0.34
Citations

In this Letter we describe the discovery of potent, selective, and orally active aminopurine JNK inhibitors. Improving the physico-chemical properties as well as increasing the potency and selectivity of a subseries with rat plasma exposure, led to the identification of four structurally diverse inhibitors. Differentiation based on PK profiles in multiple species as well as activity in a chronic efficacy model led to the identification of 1 (CC-930) as a development candidate, which is currently in Phase II clinical trial for IPF.

Bioorg.Med.Chem.Lett. 2012 Feb; 22(3):1433-1438 doi:10.1016/j.bmcl.2011.12.027

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1949521
PubMed 22244937 BMCLE8
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3TTI/0 3TTI 0 monomer 0 1 2 2706