Discovery of benzamide tetrahydro-4H-carbazol-4-ones as novel small molecule inhibitors of Hsp90

被引：78

作者：

Barta, Thomas E. ^{[1
]}

Veal, James M. ^{[1
]}

Rice, John W. ^{[1
]}

Partridge, Jeffrey M. ^{[1
]}

Fadden, R. Patrick ^{[1
]}

Ma, Wei ^{[1
]}

Jenks, Matthew ^{[1
]}

Geng, Lifeng ^{[1
]}

Hanson, Gunnar J. ^{[1
]}

Huang, Kenneth H. ^{[1
]}

Barabasz, Amy F. ^{[1
]}

Foley, Briana E. ^{[1
]}

Otto, James ^{[1
]}

Hall, Steven E. ^{[1
]}

机构：

[1] Serenex Inc, Durham, NC 27710 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 12期

关键词：

Hsp90; heat shock protein 90; cancer therapeutic; cancer inhibitor; X-ray structure; Her2; ATP; carbazol-4-one; benzamide; Hsp70;

D O I：

10.1016/j.bmcl.2008.05.023

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Hsp90 maintains the conformational stability of multiple proteins implicated in oncogenesis and has emerged as a target for chemotherapy. We report here the discovery of a novel small molecule scaffold that inhibits Hsp90. X-ray data show that the scaffold binds competitively at the ATP site on Hsp90. Cellular proliferation and client assays demonstrate that members of the series are able to inhibit Hsp90 at nanomolar concentrations. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：3517 / 3521

页数：5

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