α-Mercaptoketone based histone deacetylase inhibitors

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.

Graphical abstractThe identification and lead optimization of a novel series of α-mercaptoketone HDAC inhibitors is described.Figure optionsDownload full-size imageDownload as PowerPoint slide