2XJJ

Structure of HSP90 with small molecule inhibitor bound

2XJJ の概要

• エントリーDOI: 10.2210/pdb2xjj/pdb
• 関連するPDBエントリー: 1BYQ 1OSF 1UY6 1UY7 1UY8 1UY9 1UYC 1UYD 1UYE 1UYF 1UYG 1UYH 1UYI 1UYK 1UYL 1YC1 1YC3 1YC4 1YER 1YES 1YET 2BSM 2BT0 2BUG 2BYH 2BYI 2BZ5 2C2L 2CCS 2CCT 2CCU 2CDD 2FWY 2FWZ 2JJC 2UWD 2VCI 2VCJ 2WI1 2WI2 2WI3 2WI4 2WI5 2WI6 2WI7 2XAB 2XDK 2XDL 2XDS 2XDU 2XDX 2XHR 2XHT 2XHX 2XJG 2XJK 2XJL
• 分子名称: HEAT SHOCK PROTEIN HSP 90-ALPHA, GLYCEROL, 1,3-DIHYDROISOINDOL-2-YL-(6-HYDROXY-3,3-DIMETHYL-1,2-DIHYDROINDOL-5-YL)METHANONE, ... (4 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: 2
• 化学式量合計: 56659.64

構造登録者

Murray, C.W.,Carr, M.G.,Callaghan, O.,Chessari, G.,Congreve, M.,Cowan, S.,Coyle, J.E.,Downham, R.,Figueroa, E.,Frederickson, M.,Graham, B.,McMenamin, R.,OBrien, M.A.,Patel, S.,Phillips, T.R.,Williams, G.,Woodhead, A.J.,Woolford, A.J.A. (登録日: 2010-07-06, 公開日: 2010-08-11, 最終更新日: 2024-05-08)

主引用文献

Woodhead, A.J.,Angove, H.,Carr, M.G.,Chessari, G.,Congreve, M.,Coyle, J.E.,Cosme, J.,Graham, B.,Day, P.J.,Downham, R.,Fazal, L.,Feltell, R.,Figueroa, E.,Frederickson, M.,Lewis, J.,Mcmenamin, R.,Murray, C.W.,O'Brien, M.A.,Parra, L.,Patel, S.,Phillips, T.,Rees, D.C.,Rich, S.,Smith, D.,Trewartha, G.,Vinkovic, M.,Williams, B.,Woolford, A.J.
Discovery of (2,4-Dihydroxy-5-Isopropylphenyl)-[5-(4-Methylpiperazin-1-Ylmethyl)-1,3-Dihydroisoindol-2-Yl]Methanone (at13387), a Novel Inhibitor of the Molecular Chaperone Hsp90 by Fragment Based Drug Design.
J.Med.Chem., 53:5956-, 2010

PubMed Abstract: Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) are currently generating significant interest in clinical development as potential treatments for cancer. In a preceding publication (DOI: 10.1021/jm100059d ) we describe Astex's approach to screening fragments against Hsp90 and the subsequent optimization of two hits into leads with inhibitory activities in the low nanomolar range. This paper describes the structure guided optimization of the 2,4-dihydroxybenzamide lead molecule 1 and details some of the drug discovery strategies employed in the identification of AT13387 (35), which has progressed through preclinical development and is currently being tested in man.

PubMed: 20662534
DOI: 10.1021/JM100060B

実験手法

X-RAY DIFFRACTION (1.9 Å)