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.