Chemical phylogenetics of histone deacetylases
JE Bradner, N West, ML Grachan… - Nature chemical …, 2010 - nature.com
Nature chemical biology, 2010•nature.com
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 …
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 …
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.
nature.com