title: The structural requirements of histone deacetylase inhibitors: Suberoylanilide hydroxamic acid analogs modified at the C3 position display isoform selectivity.
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.
authors: Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
authors: Sun Ea
authors: SE
authors: Choi
authors: Sujith V W
authors: SV
authors: Weerasinghe
authors: Mary Kay H
authors: MK
authors: Pflum
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy; D020033:Protein Isoforms / Q000378:metabolism; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D020033:Protein Isoforms; D000077337:Vorinostat; D006655:Histone Deacetylases