Chapter 9

Histone Deacetylase Inhibitors: Their Structure, Function and Potential to Treat Cancer

Charles M. Marson

Abstract

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.

Total Pages: 354-425 (72)

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