The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors

被引：195

作者：

Cheung, KMJ

Matthews, TP

James, K

Rowlands, MG

Boxall, KJ

Sharp, SY

Maloney, A

Roe, SM

Prodromou, C

Pearl, LH

Aherne, GW

McDonald, E

Workman, P

机构：

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

[2] Inst Canc Res, Haddow Labs, Sutton SM2 5NG, Surrey, England

[3] Inst Canc Res, Chester Beatty Labs, Sect Struct Biol, London SW3 6JB, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 14期

基金：

英国惠康基金;

关键词：

Hsp90; inhibitors; cancer; pyrazole; resorcinol; protein crystal structure;

D O I：

10.1016/j.bmcl.2005.05.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel and potent (7.1 mu M) inhibitor of Hsp90 ATPase activity. Here, we describe the synthesis of CCT018159 and a number of close analogues together with data on their biochemical properties. Some initial structure-activity relationships are discussed, as well as the crystal structure of CCT018159 bound to Hsp90. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：3338 / 3343

页数：6

共 58 条

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