2381/42591
Christopher J. Millard
Christopher J.
Millard
Peter J. Watson
Peter J.
Watson
Louise Fairall
Louise
Fairall
John W. R. Schwabe
John W. R.
Schwabe
Targeting Class I Histone Deacetylases in a "Complex" Environment.
University of Leicester
2018
HDAC inhibitors
co-repressor complexes
gene regulation
histone deacetylases
inositol phosphates
transcription repression
Allosteric Regulation
Animals
Drug Discovery
Histone Deacetylase Inhibitors
Histone Deacetylases
Humans
Inositol Phosphates
2018-07-26 11:31:39
Journal contribution
https://figshare.le.ac.uk/articles/journal_contribution/Targeting_Class_I_Histone_Deacetylases_in_a_Complex_Environment_/10203452
Histone deacetylase (HDAC) inhibitors are proven anticancer therapeutics and have potential in the treatment of many other diseases including HIV infection, Alzheimer's disease, and Friedreich's ataxia. A problem with the currently available HDAC inhibitors is that they have limited specificity and target multiple deacetylases. Designing isoform-selective inhibitors has proven challenging due to similarities in the structure and chemistry of HDAC active sites. However, the fact that HDACs 1, 2, and 3 are recruited to several large multi-subunit complexes, each with particular biological functions, raises the possibility of specifically inhibiting individual complexes. This may be assisted by recent structural and functional information about the assembly of these complexes. Here, we review the available structural information and discuss potential targeting strategies.