PDB 2ZDU deposited: 2007-11-27 modified: 2009-02-24
Title Crystal Structure of human JNK3 complexed with an isoquinolone inhibitor
Authors Asano, Y., Aso, K., Igata, H., Itoh, F., Kawamoto, T., Kimura, H., Kitamura, S., Matsumoto, S., Ohra, T., Sogabe, S., Tamura, T., Tanaka, T., Yamaguchi, M.
Structure factors resolution 2.5 rfactor 0.241 rfree 0.319
DPI 0.91 theoretical min: 0.45

A novel series of 4-phenylisoquinolones were synthesized and evaluated as c-Jun N-terminal kinase (JNK) inhibitors. Initial modification at the 2- and 3-positions of the isoquinolone ring of hit compound 4, identified from high-throughput screening, led to the lead compound 6b. The optimization was carried out using a JNK1-binding model of 6b and several compounds exhibited potent JNK inhibition. Among them, 11g significantly inhibited cardiac hypertrophy in rat pressure-overload models without affecting blood pressure and the concept of JNK inhibitors as novel therapeutic agents for heart failure was confirmed.

Bioorg.Med.Chem. 2008 Apr; 16(8):4715-4732 doi:10.1016/j.bmc.2008.02.027

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1142440
PubMed 18313304 BMECEP
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
2ZDU/0 2ZDU 0 monomer 0 1 1 2518