2ZDU

Crystal Structure of human JNK3 complexed with an isoquinolone inhibitor

2ZDU の概要

• エントリーDOI: 10.2210/pdb2zdu/pdb
• 関連するPDBエントリー: 2ZDT
• 分子名称: 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)
• 機能のキーワード: protein kinase, alternative splicing, atp-binding, chromosomal rearrangement, cytoplasm, epilepsy, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P53779
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42623.07

構造登録者

Sogabe, S.,Ohra, T.,Itoh, F.,Habuka, N.,Fujishima, A. (登録日: 2007-11-27, 公開日: 2008-09-23, 最終更新日: 2023-11-01)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.5 Å)