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HDAC Inhibitors and Other Histone Modifying Natural Products as Emerging Anticancer Agents

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Natural Products and Cancer Drug Discovery

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Histone deacetylase (HDAC) inhibitors represent a new class of anticancer agents that target dysregulated acetylation of histone lysines, an epigenetic rather than a genetic event. Certain HDACs are overexpressed and hyperactive in cancer cells, and suppression of these enzymes’ activities provides superior selectivity over more traditional anticancer agents. To date, two HDAC inhibitors—vorinostat and romidepsin—have reached the market, with romidepsin being an actual natural product and vorinostat closely related to the natural product HDAC inhibitor trichostatin A. Over the past 15 years, several secondary metabolites with high structural diversity from microorganisms, marine sponges, and cyanobacteria have been discovered to possess HDAC inhibitory activity and are currently at the clinical and preclinical stages. In this chapter, we recapitulate the discovery of natural product HDAC inhibitors, enumerate the challenges in their development and provide insights in the continuing role of natural products in the discovery of HDAC inhibitors as well as new modulators for other clinically-relevant epigenetic events, including histone methylation.

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Acknowledgments

Natural products research in the authors’ laboratory is supported by the National Institutes of Health, NIGMS grant P41GM806210 and NCI grants R01CA138544 and R21CA133681, and the Bankhead-Coley Cancer Research Program, grant 1BG07.

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  1. Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, FL, 32610, USA

    Lilibeth A. Salvador & Hendrik Luesch

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Correspondence to Hendrik Luesch .

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    Frank E. Koehn

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Salvador, L.A., Luesch, H. (2013). HDAC Inhibitors and Other Histone Modifying Natural Products as Emerging Anticancer Agents. In: Koehn, F. (eds) Natural Products and Cancer Drug Discovery. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4654-5_4

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