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Mol Pharmacol. 2005 Oct;68(4):917-32. Epub 2005 Jun 14.

Rational development of histone deacetylase inhibitors as anticancer agents: a review.

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  • 1Clinical Pharmacology Research Core, National Cancer Institute, Bethesda, MD 20892, USA.

Abstract

The epigenome is defined by DNA methylation patterns and the associated post-translational modifications of histones. This histone code determines the expression status of individual genes dependent upon their localization on the chromatin. The histone deacetylases (HDACs) play a major role in keeping the balance between the acetylated and deacetylated states of chromatin and eventually regulate gene expression. Recent developments in understanding the cancer cell cycle, specifically the interplay with chromatin control, are providing opportunities for developing mechanism-based therapeutic drugs. Inhibitors of HDACs are under considerable exploration, in part because of their potential roles in reversing the silenced genes in transformed tumor cells by modulating transcriptional processes. This review is an effort to summarize the nonclinical and clinical status of HDAC inhibitors currently under development in anticancer therapy.

PMID:
15955865
[PubMed - indexed for MEDLINE]
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