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Chemical phylogenetics of histone deacetylases

  作者 BRADNER JAMES E; WEST NATHAN; GRACHAN MELISSA L; GREENBERG EDWARD F; HAGGARTY STEPHEN J; WARNOW TANDY; MAZITSCHEK RALPH  
  选自 期刊  NATURE CHEMICAL BIOLOGY;  卷期  2010年6-3;  页码  238-243  
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[摘要]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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