Chemical phylogenetics of histone deacetylases

James E. Bradner, Nathan West, Melissa L. Grachan, Edward F. Greenberg, Stephen J. Haggarty, Tandy Warnow, Ralph Mazitschek

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)238-243
Number of pages6
JournalNature chemical biology
Issue number3
StatePublished - Mar 2010
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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