|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Bradner, JE, West, N, Grachan, ML, Greenberg, EF, Haggarty, SJ, Warnow, T, Mazitschek, R|
|Journal||Nature chemical biology|
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.