title: The structural requirements of histone deacetylase inhibitors: suberoylanilide hydroxamic acid analogs modified at the C6 position.
abstract: Suberoylanilide hydroxamic acid (SAHA, Vorinostat), the first FDA-approved histone deacetylase (HDAC) inhibitor drug, was modified at the C6 position to study the structural requirements for high potency and selectivity. Substituents on the C6 position only modestly influenced inhibitor potency, with poorer activity observed as substituent size increased. Interestingly, C6 substituents also modestly influenced selectivity compared to the parent compound, SAHA. This systematic study documenting the influence of substituents on the SAHA linker region will aid development of anti-cancer drugs targeting HDAC proteins.
authors.affiliation: Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Sun Ea
authors.initials: SE
authors.lastname: Choi
authors.forename: Mary Kay H
authors.initials: MK
authors.lastname: Pflum
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D002244:Carbon / Q000737:chemistry; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000077337:Vorinostat; D000099186:Histone Deacetylase 3
chemical_list: D000970:Antineoplastic Agents; D002244:Carbon; D056284:Histone Deacetylase 1; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D000077337:Vorinostat; D000099186:Histone Deacetylase 3; C433811:HDAC6 protein, human