Chemical phylogenetics of histone deacetylases.

Nat Chem Biol
Authors
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.

Year of Publication
2010
Journal
Nat Chem Biol
Volume
6
Issue
3
Pages
238-243
Date Published
2010 Mar
ISSN
1552-4469
URL
DOI
10.1038/nchembio.313
PubMed ID
20139990
PubMed Central ID
PMC2822059
Links
Grant list
N01 / HL / NHLBI NIH HHS / United States
P01 CA078048-08 / CA / NCI NIH HHS / United States
K08 CA128972-02 / CA / NCI NIH HHS / United States
N01-C0-012400 / CO / NCI NIH HHS / United States
T32 CA079443-08 / CA / NCI NIH HHS / United States
T32 CA079443 / CA / NCI NIH HHS / United States
K08 CA128972-02S1 / CA / NCI NIH HHS / United States
K08 CA128972-01A1 / CA / NCI NIH HHS / United States
P01 CA078048-09 / CA / NCI NIH HHS / United States
P01 CA078048-10 / CA / NCI NIH HHS / United States
R01 DA028301-01 / DA / NIDA NIH HHS / United States
K08 CA128972 / CA / NCI NIH HHS / United States
N01-C0-012400 / PHS HHS / United States
N01CO12400 / CA / NCI NIH HHS / United States
P01 CA078048 / CA / NCI NIH HHS / United States
R01 DA028301 / DA / NIDA NIH HHS / United States