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Nat Chem Biol. 2010 Mar;6(3):238-243. Epub 2010 Feb 7.

Chemical phylogenetics of histone deacetylases.

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[1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Chemical Biology Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.


The broad study of histone deacetylases in chemistry, biology and medicine relies on tool compounds to derive mechanistic insights. A phylogenetic analysis of class I and II histone deacetylases (HDACs) as targets of a comprehensive, structurally diverse panel of inhibitors revealed unexpected isoform selectivity even among compounds widely perceived as nonselective. The synthesis and study of a focused library of cinnamic hydroxamates allowed the identification of, to our knowledge, the first nonselective HDAC inhibitor. These data will guide a more informed use of HDAC inhibitors as chemical probes and therapeutic agents.

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