Carbonyl- and sulfur-containing analogs of suberoylanilide hydroxamic acid: Potent inhibition of histone deacetylases

被引：38

作者：

Gu, WX

Nusinzon, I

Smith, RD

Horvath, CM

Silverman, RB ^{[1
]}

机构：

[1] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA

[2] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA

[3] Evanston Northwestern Healthcare, Dept Med, Evanston, IL 60201 USA

[4] Northwestern Univ, Ctr Drug Discovery & Chem Biol, Chicago, IL 60611 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2006年 / 14卷 / 10期

关键词：

histone deacetylase; inhibitors; alpha-mercaptoketone; suberoylanilide hydroxamic acid; SAHA; alpha-thioacetoxyketone;

D O I：

10.1016/j.bmc.2005.12.047

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylase, is used in clinical trials for a variety of advanced cancers. Twelve new analogs of SAHA were synthesized and tested as in vitro inhibitors of isolated histone deacetylases (HDACS) and in vivo inhibitors of interferon regulated transcriptional responses (a marker for HDAC activity). The analogs containing an alpha-mercaptoketone or an alpha-thioacetoxyketone were more potent than SAHA in both assays. (c) 2006 Elsevier Ltd. All rights reserved.

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页码：3320 / 3329

页数：10

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