Fragment-based Identification of Hsp90 Inhibitors

被引：43

作者：

Barker, John J. ^{[1
]}

Barker, Oliver ^{[1
]}

Boggio, Roberto ^{[2
]}

Chauhan, Viddhata ^{[1
]}

Cheng, Robert K. Y. ^{[1
]}

Corden, Vincent ^{[1
]}

Courtney, Stephen M. ^{[1
]}

Edwards, Neil ^{[1
]}

Falque, Virginie M. ^{[1
]}

Fusar, Fulvia ^{[3
]}

Gardiner, Mihaly ^{[1
]}

Hamelin, Estelle M. N. ^{[1
]}

Hesterkamp, Thomas ^{[1
]}

Ichihara, Osamu ^{[1
]}

Jones, Richard S. ^{[1
]}

Mather, Owen ^{[1
]}

Mercurio, Ciro ^{[3
]}

Minucci, Saverio ^{[4
,5
]}

Montalbetti, Christian A. G. N. ^{[1
]}

Mueller, Annett ^{[1
]}

Patel, Deepti ^{[1
]}

Phillips, Banu G. ^{[1
]}

Varasi, Mario ^{[3
]}

Whittaker, Mark ^{[1
]}

Winkler, Dirk ^{[1
]}

Yarnold, Christopher J. ^{[1
]}

机构：

[1] Evotec, Abingdon OX10 4SA, Oxon, England

[2] Congenia Srl, Genextra Grp, I-20139 Milan, Italy

[3] DAC Srl, Genextra Grp, I-20139 Milan, Italy

[4] Univ Milan, Dept Biomol Sci & Biotechnol, I-20139 Milan, Italy

[5] European Inst Oncol, Dept Expt Oncol, I-20139 Milan, Italy

来源：

CHEMMEDCHEM | 2009年 / 4卷 / 06期

关键词：

fragment-based screening; Hsp90; oximes; structure-based drug design; tetrahydrobenzopyrimidine; PHASE-I TRIAL; HEAT-SHOCK-PROTEIN-90; INHIBITOR; PEDIATRIC-PATIENTS; SOLID TUMORS; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; DISCOVERY; PROTEIN; POTENT;

D O I：

10.1002/cmdc.200900011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

(Chemical Equation Presented) Heat shock protein 90 (Hsp90) plays a key role in stress response and protection of the cell against the effects of mutation. Herein we report the identification of an Hsp90 inhibitor identified by fragment screening using a high-concentration biochemical assay, as well as its optimisation by in silico searching coupled with a structure-based drug design (SBDD) approach. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：963 / 966

页数：4

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