7LSZ

Hsp90a N-terminal inhibitor

7LSZ の概要

• エントリーDOI: 10.2210/pdb7lsz/pdb
• 分子名称: Heat shock protein HSP 90-alpha, {3-[(2,3-dihydro-1,4-benzodioxin-6-yl)sulfanyl]-4-hydroxyphenyl}(1,3-dihydro-2H-isoindol-2-yl)methanone (3 entities in total)
• 機能のキーワード: inhibitor, hsp90a, chaperone
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33905.70

構造登録者

Balch, M.,Peng, S.,Deng, J.,Matts, R. (登録日: 2021-02-18, 公開日: 2021-03-03, 最終更新日: 2023-10-18)

主引用文献

Mishra, S.J.,Khandelwal, A.,Banerjee, M.,Balch, M.,Peng, S.,Davis, R.E.,Merfeld, T.,Munthali, V.,Deng, J.,Matts, R.L.,Blagg, B.S.J.
Selective Inhibition of the Hsp90 alpha Isoform.
Angew.Chem.Int.Ed.Engl., 60:10547-10551, 2021

PubMed Abstract: The 90 kDa heat shock protein (Hsp90) is a molecular chaperone that processes nascent polypeptides into their biologically active conformations. Many of these proteins contribute to the progression of cancer, and consequently, inhibition of the Hsp90 protein folding machinery represents an innovative approach toward cancer chemotherapy. However, clinical trials with Hsp90 N-terminal inhibitors have encountered deleterious side effects and toxicities, which appear to result from the pan-inhibition of all four Hsp90 isoforms. Therefore, the development of isoform-selective Hsp90 inhibitors is sought to delineate the pathological role played by each isoform. Herein, we describe a structure-based approach that was used to design the first Hsp90α-selective inhibitors, which exhibit >50-fold selectivity versus other Hsp90 isoforms.

PubMed: 33621416
DOI: 10.1002/anie.202015422

実験手法

X-RAY DIFFRACTION (1.7 Å)