title: Aminosuberoyl hydroxamic acids (ASHAs): a potent new class of HDAC inhibitors.
abstract: Histone deacetylase (HDAC) inhibitors that target Class I and Class II HDACs are currently in advanced clinical trials for the treatment of cancer. Vorinostat (Zolinza, SAHA) is a hydroxamic acid approved for the treatment of patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. As part of an on-going effort to better understand the nature of the HDAC enzyme/inhibitor interaction and design highly effective HDAC inhibitors, we herein report the design, synthesis and HDAC inhibitory activity of a vorinostat-derived series of substrate-based HDAC inhibitors.
authors.affiliation: Merck Research Laboratories, Departments of Drug Design & Optimization and Cancer & Biology Therapeutics, 33 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Sandro
authors.initials: S
authors.lastname: Belvedere
authors.forename: David J
authors.initials: DJ
authors.lastname: Witter
authors.forename: Jiaming
authors.initials: J
authors.lastname: Yan
authors.forename: J Paul
authors.initials: JP
authors.lastname: Secrist
authors.forename: Victoria
authors.initials: V
authors.lastname: Richon
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Miller
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids