2ZDU

Crystal Structure of human JNK3 complexed with an isoquinolone inhibitor

Summary for 2ZDU

• Entry DOI: 10.2210/pdb2zdu/pdb
• Related: 2ZDT
• Descriptor: Mitogen-activated protein kinase 10, 4-[(4-{[6-bromo-3-(methoxycarbonyl)-1-oxo-4-phenylisoquinolin-2(1H)-yl]methyl}phenyl)amino]-4-oxobutanoic acid (3 entities in total)
• Functional Keywords: protein kinase, alternative splicing, atp-binding, chromosomal rearrangement, cytoplasm, epilepsy, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P53779
• Total number of polymer chains: 1
• Total formula weight: 42623.07

Authors

Sogabe, S.,Ohra, T.,Itoh, F.,Habuka, N.,Fujishima, A. (deposition date: 2007-11-27, release date: 2008-09-23, Last modification date: 2023-11-01)

Primary citation

Asano, Y.,Kitamura, S.,Ohra, T.,Aso, K.,Igata, H.,Tamura, T.,Kawamoto, T.,Tanaka, T.,Sogabe, S.,Matsumoto, S.,Yamaguchi, M.,Kimura, H.,Itoh, F.
Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1)
Bioorg.Med.Chem., 16:4715-4732, 2008

PubMed Abstract: 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.

PubMed: 18313304
DOI: 10.1016/j.bmc.2008.02.027

Experimental method

X-RAY DIFFRACTION (2.5 Å)