Discovery of a Potent Class I Selective Ketone Histone Deacetylase Inhibitor with Antitumor Activity in Vivo and Optimized Pharmacokinetic Properties
IRBM/Merck Research Laboratories, Via Pontina km 30,600, 00040 Pomezia, Italy
J. Med. Chem., 2009, 52 (11), pp 3453–3456
DOI: 10.1021/jm9004303
Abstract
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The optimization of a potent, class I selective ketone HDAC inhibitor is shown. It possesses optimized pharmacokinetic properties in preclinical species, has a clean off-target profile, and is negative in a microbial mutagenicity (Ames) test. In a mouse xenograft model it shows efficacy comparable to that of vorinostat at a 10-fold reduced dose.
Supporting Information
Complete experimental procedures and characterization data. This material is available free of charge via the Internet at http://pubs.acs.org.
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