3K98

HSP90 N-terminal domain in complex with (1R)-2-(5-chloro-2,4-dihydroxybenzoyl)-N-ethylisoindoline-1-carboxamide

3K98 の概要

• エントリーDOI: 10.2210/pdb3k98/pdb
• 関連するPDBエントリー: 3K97 3K99
• 分子名称: Heat shock protein HSP 90-alpha, (1R)-2-[(5-chloro-2,4-dihydroxyphenyl)carbonyl]-N-ethyl-2,3-dihydro-1H-isoindole-1-carboxamide, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: hsp90, atp binding domain, inhibition, acetylation, alternative splicing, atp-binding, chaperone, cytoplasm, nucleotide-binding, phosphoprotein, stress response
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P07900
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53640.01

構造登録者

Gajiwala, K.S.,Davies II, J.F. (登録日: 2009-10-15, 公開日: 2010-02-09, 最終更新日: 2024-02-21)

主引用文献

Kung, P.P.,Huang, B.,Zhang, G.,Zhou, J.Z.,Wang, J.,Digits, J.A.,Skaptason, J.,Yamazaki, S.,Neul, D.,Zientek, M.,Elleraas, J.,Mehta, P.,Yin, M.J.,Hickey, M.J.,Gajiwala, K.S.,Rodgers, C.,Davies, J.F.,Gehring, M.R.
Dihydroxyphenylisoindoline amides as orally bioavailable inhibitors of the heat shock protein 90 (hsp90) molecular chaperone.
J.Med.Chem., 53:499-503, 2010

PubMed Abstract: The discovery and optimization of potency and metabolic stability of a novel class of dihyroxyphenylisoindoline amides as Hsp90 inhibitors are presented. Optimization of a screening hit using structure-based design and modification of log D and chemical structural features led to the identification of a class of orally bioavailable non-quinone-containing Hsp90 inhibitors. This class is exemplified by 14 and 15, which possess improved cell potency and pharmacokinetic profiles compared with the original screening hit.

PubMed: 19908836
DOI: 10.1021/jm901209q

実験手法

X-RAY DIFFRACTION (2.4 Å)