α-Mercaptoketone based histone deacetylase inhibitors

PL Wash, TZ Hoffman, BM Wiley, C Bonnefous…

Index: Wash, Paul L.; Hoffman, Timothy Z.; Wiley, Brandon M.; Bonnefous, Celine; Smith, Nicholas D.; Sertic, Michael S.; Lawrence, Charles M.; Symons, Kent T.; Nguyen, Phan-Manh; Lustig, Kevin D.; Guo, Xin; Annable, Tami; Noble, Stewart A.; Hager, Jeffrey H.; Hassig, Christian A.; Malecha, James W. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 24 p. 6482 - 6485

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Citation Number: 6

Abstract

In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel α-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, α-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo.