Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design

被引：197

作者：

Dymock, BW

Barril, X

Brough, PA

Cansfield, JE

Massey, A

McDonald, E

Hubbard, RE

Surgenor, A

Roughley, SD

Webb, P

Workman, P

Wright, L

Drysdale, MJ

机构：

[1] Vernalis Ltd, Cambridge CB1 6GB, England

[2] Inst Canc Res, Canc Res UK Ctr Canc Therapeut, Sutton SM2 5NG, Surrey, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 13期

关键词：

D O I：

10.1021/jm050355z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues. These exhibit enhanced potency against the target in binding and functional assays with accompanying appropriate cellular pharmaeodynamic changes. Compound 11 (VER-49009) compares favorably with the clinically evaluated 17-AAG.

引用

页码：4212 / 4215

页数：4

共 27 条

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