Recent advances in the discovery of small molecule histone deacetylase inhibitors.

The reversible acetylation of lysine amino groups in nuclear histones is an important mechanism by which gene expression is regulated, and may act by disrupting higher order chromatin structure. In normal cells, the competing activities of two enzyme classes, the histone acetyl transferases (HATs) and histone deacetylases (HDACs), result in cell-specific patterns of gene expression. Aberrant patterns of histone acetylation have been linked to cancer, and natural and synthetic HDAC inhibitors (HDAIs) have shown antiproliferative effects on tumor cells in culture. Thus, there has been an increasing interest in histone deacetylase inhibitors as novel anticancer agents, with clinical investigation underway for several molecules. This review summarizes recent progress in the development of new HDAIs and their reported activities.