4BQJ

structure of HSP90 with an inhibitor bound

4BQJ の概要

• エントリーDOI: 10.2210/pdb4bqj/pdb
• 関連するPDBエントリー: 4BQG
• 分子名称: HEAT SHOCK PROTEIN HSP 90-ALPHA, 5-[2,4-dihydroxy-6-(4-nitrophenoxy)phenyl]-N-ethyl-1,2-oxazole-3-carboxamide (3 entities in total)
• 機能のキーワード: hydrolase
• 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: 26196.26

構造登録者

Casale, E.,Brasca, M.G.,Mantegani, S.,Amboldi, N.,Bindi, S.,Caronni, D.,Ceccarelli, W.,Colombo, N.,DePonti, A.,Donati, D.,Ermoli, A.,Fachin, G.,Felder, E.R.,Ferguson, R.D.,Fiorelli, C.,Guanci, M.,Isacchi, A.,Pesenti, E.,Polucci, P.,Riceputi, L.,Sola, F.,Visco, C.,Zuccotto, F.,Fogliatto, G. (登録日: 2013-05-30, 公開日: 2013-10-23, 最終更新日: 2024-05-08)

主引用文献

Brasca, M.G.,Mantegani, S.,Amboldi, N.,Bindi, S.,Caronni, D.,Casale, E.,Ceccarelli, W.,Colombo, N.,De Ponti, A.,Donati, D.,Ermoli, A.,Fachin, G.,Felder, E.R.,Ferguson, R.D.,Fiorelli, C.,Guanci, M.,Isacchi, A.,Pesenti, E.,Polucci, P.,Riceputi, L.,Sola, F.,Visco, C.,Zuccotto, F.,Fogliatto, G.
Discovery of Nms-E973 as Novel, Selective and Potent Inhibitor of Heat Shock Protein 90 (Hsp90).
Bioorg.Med.Chem., 21:7047-, 2013

PubMed Abstract: Novel small molecule inhibitors of heat shock protein 90 (Hsp90) were discovered with the help of a fragment based drug discovery approach (FBDD) and subsequent optimization with a combination of structure guided design, parallel synthesis and application of medicinal chemistry principles. These efforts led to the identification of compound 18 (NMS-E973), which displayed significant efficacy in a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed in vivo by typical modulation of known Hsp90 client proteins, and with a favorable pharmacokinetic and safety profile.

PubMed: 24100158
DOI: 10.1016/J.BMC.2013.09.018

実験手法

X-RAY DIFFRACTION (2 Å)