4CWP

Human HSP90 alpha N-terminal domain in complex with an Aminotriazoloquinazoline inhibitor

4CWP の概要

• エントリーDOI: 10.2210/pdb4cwp/pdb
• 関連するPDBエントリー: 4CWF 4CWN 4CWO 4CWQ 4CWR 4CWS 4CWT
• 分子名称: HEAT SHOCK PROTEIN HSP 90-ALPHA, 5-(1,3-benzodioxol-5-ylmethyl)[1,2,4]triazolo[1,5-c]quinazolin-2-amine (3 entities in total)
• 機能のキーワード: chaperone
• 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: 1
• 化学式量合計: 26130.25

構造登録者

Casale, E.,Amboldi, N.,Brasca, G.,Caronni, D.,Colombo, N.,Dalvit, C.,Felder, E.R.,Fogliatto, G.,Isacchi, A.,Mantegani, S.,Polucci, P.,Riceputi, L.,Sola, F.,Visco, C.,Zuccotto, F.,Casuscelli, F. (登録日: 2014-04-03, 公開日: 2014-07-09, 最終更新日: 2024-05-08)

主引用文献

Casale, E.,Amboldi, N.,Brasca, M.G.,Caronni, D.,Colombo, N.,Dalvit, C.,Felder, E.R.,Fogliatto, G.,Galvani, A.,Isacchi, A.,Polucci, P.,Riceputi, L.,Sola, F.,Visco, C.,Zuccotto, F.,Casuscelli, F.
Fragment-Based Hit Discovery and Structure-Based Optimization of Aminotriazoloquinazolines as Novel Hsp90 Inhibitors.
Bioorg.Med.Chem., 22:4135-, 2014

PubMed Abstract: In the last decade the heat shock protein 90 (Hsp90) has emerged as a major therapeutic target and many efforts have been dedicated to the discovery of Hsp90 inhibitors as new potent anticancer agents. Here we report the identification of a novel class of Hsp90 inhibitors by means of a biophysical FAXS-NMR based screening of a library of fragments. The use of X-ray structure information combined with modeling studies enabled the fragment evolution of the initial triazoloquinazoline hit to a class of compounds with nanomolar potency and drug-like properties suited for further lead optimization.

PubMed: 24980703
DOI: 10.1016/J.BMC.2014.05.056

実験手法

X-RAY DIFFRACTION (1.95 Å)