The structural requirements of histone deacetylase inhibitors: Suberoylanilide hydroxamic acid analogs modified at the C3 position display isoform selectivity

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Choi, Sun Ea¹  Weerasinghe, Sujith V. W.¹  Pflum, Mary Kay H.¹ 

[1] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA

关键词: Histone deaceylases;    HDAC inhibitors;    Vorinostat;    Isoform selectivity;   

DOI  :  10.1016/j.bmcl.2011.08.027

来源: Elsevier

【 摘 要 】

The FDA-approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat) was modified to improve its selectivity for a single histone deaetylase (HDAC) isoform. We show that attaching an ethyl group at the C3 position transforms SAHA from nonselective to an HDAC6-selective inhibitor. Theses results indicate that small structural changes in SAHA can significantly influence selectivity, which will lead future anticancer design efforts targeting HDAC proteins. (C) 2011 Elsevier Ltd. All rights reserved.

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