5X5O

Crystal structure of ZAK in complex with compound D2829

5X5O の概要

• エントリーDOI: 10.2210/pdb5x5o/pdb
• 分子名称: Mitogen-activated protein kinase kinase kinase MLT, N-[2,4-bis(fluoranyl)-3-[2-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]phenyl]-3-bromanyl-benzenesulfonamide (3 entities in total)
• 機能のキーワード: zak, kinase, inhibitor, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : Q9NYL2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35856.82

構造登録者

Dai, Y.B.,Zhao, P.,Yun, C.H. (登録日: 2017-02-17, 公開日: 2017-12-27, 最終更新日: 2024-03-27)

主引用文献

Chang, Y.,Lu, X.,Shibu, M.A.,Dai, Y.B.,Luo, J.,Zhang, Y.,Li, Y.,Zhao, P.,Zhang, Z.,Xu, Y.,Tu, Z.C.,Zhang, Q.W.,Yun, C.H.,Huang, C.Y.,Ding, K.
Structure Based Design of N-(3-((1H-Pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides as Selective Leucine-Zipper and Sterile-alpha Motif Kinase (ZAK) Inhibitors.
J. Med. Chem., 60:5927-5932, 2017

PubMed Abstract: A series of N-(3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides were designed as the first class of highly selective ZAK inhibitors. The representative compound 3h strongly inhibits the kinase activity of ZAK with an IC of 3.3 nM and dose-dependently suppresses the activation of ZAK downstream signals in vitro and in vivo, while it is significantly less potent for the majority of 403 nonmutated kinases evaluated. Compound 3h also exhibits orally therapeutic effects on cardiac hypertrophy in a spontaneous hypertensive rat model.

PubMed: 28586211
DOI: 10.1021/acs.jmedchem.7b00572

実験手法

X-RAY DIFFRACTION (1.868 Å)