Aminosuberoyl hydroxamic acids (ASHAs): a potent new class of HDAC inhibitors.
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.
Belvedere
Sandro
S
Merck Research Laboratories, Departments of Drug Design & Optimization and Cancer & Biology Therapeutics, 33 Avenue Louis Pasteur, Boston, MA 02115, USA.
Witter
David J
DJ
Yan
Jiaming
J
Secrist
J Paul
JP
Richon
Victoria
V
Miller
Thomas A
TA
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids