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.
Keywords: Histone deacetylase (HDAC), HDAC isoform, histone deacetylase inhibitor, cancer therapy, hydroxamate, zinc-binding group, benzamide, cyclic peptide
Anti-Cancer Agents in Medicinal Chemistry
Title: Histone Deacetylase Inhibitors: Design, Structure-Activity Relationships and Therapeutic Implications for Cancer
Volume: 9 Issue: 6
Author(s): Charles M. Marson
Affiliation:
Keywords: Histone deacetylase (HDAC), HDAC isoform, histone deacetylase inhibitor, cancer therapy, hydroxamate, zinc-binding group, benzamide, cyclic peptide
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.
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Cite this article as:
Marson M. Charles, Histone Deacetylase Inhibitors: Design, Structure-Activity Relationships and Therapeutic Implications for Cancer, Anti-Cancer Agents in Medicinal Chemistry 2009; 9 (6) . https://dx.doi.org/10.2174/187152009788679976
DOI https://dx.doi.org/10.2174/187152009788679976 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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