Histone deacetylase enzymes (HDACs) are epigenetic regulators that remove
acetyl groups from the tails of lysine residues of histone protein in nuclear chromatin
and also deacetylate some other non-histone proteins. HDACs and histone
acetyltransferases (HATs) are major regulators of cellular protein acetylation status; an
imbalance in acetylation levels, particularly under-acetylated (hypoacetylated) histone
protein has been associated with precancerous or malignant states, arising in part
through transcriptional repression induced by regions of condensed chromatin
containing non-acetylated, protonated, lysine termini closely bound to DNA phosphate
residues. Small-molecule inhibitors of HDACs relieve this transcriptional repression
and some are used as clinical anti-cancer agents. The epigenetic level of action of
HDAC inhibitors can make them effective against cancers that are refractory to
conventional tretament. This review surveys recent developments in the design,
structures and biological properties of HDAC inhibitors in the context of potential
cancer therapy.
Keywords: Histone deacetylase (HDAC), HDAC isoform selectivity, histone
deacetylase inhibitor, cancer therapy, hydroxamic acid, zinc-binding group,
benzamide.
