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Chemical phylogenetics of histone deacetylases.

ABSTRACT: 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.

SUBMITTER: Bradner JE

PROVIDER: S-EPMC2822059 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Chemical phylogenetics of histone deacetylases.

Bradner James E JE West Nathan N Grachan Melissa L ML Greenberg Edward F EF Haggarty Stephen J SJ Warnow Tandy T Mazitschek Ralph R

Nature chemical biology 20100207 3

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 n ...[more]

PMID: 20139990

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