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

  • Bioorg Med Chem Lett. 2011 Oct 15;21(20):6139-42. doi: 10.1016/j.bmcl.2011.08.027.
Sun Ea Choi  1 ,  Sujith V W Weerasinghe ,  Mary Kay H Pflum
Affiliations
  • 1. Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
PMID: 21889343 DOI: 10.1016/j.bmcl.2011.08.027
Abstract

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 anti-cancer design efforts targeting HDAC proteins.