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Histone Deacetylases: the Biology and Clinical Implication pp 241–255Cite as

Sirtuin Modulators

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 206))

Abstract

Members of the sirtuin family including the founding protein Sir2 in Saccharomyces cerevisiae have been linked to lifespan extension in simple organisms. This finding prompted evaluation of the role of Sir2 orthologues in many aging-associated conditions including neurodegeneration, type II diabetes and cancer. These studies have demonstrated that genetic and pharmacologic manipulation of sirtuin activity have beneficial effects in a surprisingly broad spectrum of aging-associated conditions suggesting that the Sir2-family of enzymes presents an attractive target for the development of pharmacological agents. While the initial model favored pharmacological activators of sirtuins as calorie restriction mimetics, it now appears that either activation or inhibition of sirtuins may be desirable for ameliorating disease depending on the pathological condition and the target tissue. In this chapter we review the development of pharmacological small molecule activators and inhibitors of the sirtuin family of enzymes.

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Ackowledgments

This work was supported by the National Institute of Health grant CA129132 to AB.

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA

    Sumit S. Mahajan, Vid Leko, Julian A. Simon & Antonio Bedalov

Authors
  1. Sumit S. Mahajan
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  2. Vid Leko
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  3. Julian A. Simon
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  4. Antonio Bedalov
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Corresponding author

Correspondence to Antonio Bedalov .

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Editors and Affiliations

  1. , Department of Pharmacology, Duke University, Durham, 27710, North Carolina, USA

    Tso-Pang Yao

  2. , Department of Molecular Oncology, H.Lee Moffitt Cancer Center & Research I, Magnolia Drive 12902, Tampa, 33612, Florida, USA

    Edward Seto

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© 2011 Springer-Verlag Berlin Heidelberg

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Mahajan, S.S., Leko, V., Simon, J.A., Bedalov, A. (2011). Sirtuin Modulators. In: Yao, TP., Seto, E. (eds) Histone Deacetylases: the Biology and Clinical Implication. Handbook of Experimental Pharmacology, vol 206. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21631-2_11

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