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Bioorg Med Chem Lett. 2007 Jul 15;17(14):3969-71. Epub 2007 Apr 29.

Aminosuberoyl hydroxamic acids (ASHAs): a potent new class of HDAC inhibitors.

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Merck Research Laboratories, Departments of Drug Design & Optimization and Cancer & Biology Therapeutics, 33 Avenue Louis Pasteur, Boston, MA 02115, USA.


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.

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