Summary
PDB 2ZDT deposited: 2007-11-27 modified: 2011-07-13
Title Crystal Structure of human JNK3 complexed with an isoquinolone inhibitor
Authors Asano, Y., Fukumoto, S., Igata, H., Ikeda, S., Itoh, F., Kajino, M., Kaneko, M., Kawamoto, T., Kimura, H., Kitamura, S., Matsumoto, S., Ohra, T., Sogabe, S., Tamura, T., Tanaka, T., Yamaguchi, M.
Method X-RAY DIFFRACTION
Structure factors resolution 2.0 rfactor 0.216 rfree 0.262
DPI 0.47 theoretical min: 0.21
Citations

3-Metoxycarbonyl isoquinolone derivative 1 has been identified as a potent JNK inhibitor and significantly inhibited cardiac hypertrophy in a rat pressure-overload model. Herein, a series of isoquinolones with an imidazolylmethyl or a pyrazolylmethyl group at the 2-position were designed based on X-ray crystallographic analysis of the complex between the isoquinolone compound and JNK3, as wells as the relationship between compound lipophilicity (logD) and activity in a cell-based assay. The compounds prepared showed potent JNK1 inhibitory activities in a cell-based assay. Among them the isoquinolone derivative possessing 5-[(cyclopropylamino)carbonyl]-1-methyl-1H-pyrazole (16e) exhibited significant anti-hypertrophic activity at doses of more than 1mg/kg (po) in a pressure-overload model.

Bioorg.Med.Chem. 2008 Apr; 16(8):4699-4714 doi:10.1016/j.bmc.2008.02.028

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1144699
PubMed 18313930 BMECEP
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
2ZDT/0 2ZDT 0 monomer 0 1 2 2677