title: Histone deacetylase inhibitors: design, structure-activity relationships and therapeutic implications for cancer.
abstract: Histone deacetylases (HDACs) remove acetyl groups from the tails of lysine residues of histone protein in nuclear chromatin and also from acetylated sites in non-histone proteins. HDACs and histone acetyltransferases (HATs) are major influences on the level of cellular protein acetylation, and an imbalance in acetylation levels, particularly under-acetylated (hypoacetylated) histone protein has been associated with precancerous or malignant states. Consequently, small molecule inhibitors of HDACs have been synthesised and some now form a newly emerging class of anti-cancer agents that can regulate transcription and inhibit proliferation of cancer cells by inducing cell cycle arrest, differentiation and/or apoptosis, among other major biological phenomena. The different mechanism(s) of action of HDAC inhibitors compared to conventional anti-neoplastic agents provides a possibility that HDAC inhibitors may be effective for refractory cancers. Accordingly, a number of programs for the development of HDAC inhibitors as anti-cancer drugs have been initiated. This review highlights recent developments in the design, synthesis and biological properties of HDAC inhibitors in the context of potential cancer therapy.
authors: Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London WC1HOAJ, UK. c.m.marson@ucl.ac.uk
authors: Charles M
authors: CM
authors: Marson
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases