Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes

Jill C. Milne, Philip D. Lambert, Simon Schenk, David P. Carney, Jesse J. Smith, David J. Gagne, Lei Jin, Olivier Boss, Robert B. Perni, Chi B. Vu, Jean E. Bemis, Roger Xie, Jeremy S. Disch, Pui Yee Ng, Joseph J. Nunes, Amy V. Lynch, Hongying Yang, Heidi Galonek, Kristine Israelian, Wendy Choy, Andre Iffland, Siva Lavu, Oliver Medvedik, David A. Sinclair, Jerrold M. Olefsky, Michael R. Jirousek, Peter J. Elliott and Christoph H. Westphal ()
Additional contact information
Jill C. Milne: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Philip D. Lambert: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Simon Schenk: University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
David P. Carney: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Jesse J. Smith: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
David J. Gagne: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Lei Jin: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Olivier Boss: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Robert B. Perni: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Chi B. Vu: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Jean E. Bemis: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Roger Xie: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Jeremy S. Disch: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Pui Yee Ng: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Joseph J. Nunes: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Amy V. Lynch: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Hongying Yang: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Heidi Galonek: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Kristine Israelian: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Wendy Choy: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Andre Iffland: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Siva Lavu: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Oliver Medvedik: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
David A. Sinclair: Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
Jerrold M. Olefsky: University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Michael R. Jirousek: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Peter J. Elliott: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Christoph H. Westphal: Sirtris Pharmaceuticals Inc., 790 Memorial Drive, Cambridge, Massachusetts 02139, USA

Nature, 2007, vol. 450, issue 7170, 712-716

Abstract: SIRT1 activators in diabetes SIRT1, an NAD+-dependent deacetylase that acts on proteins involved in cellular regulation, has been implicated in longevity and as a mediator of the beneficial effects of calorie restriction. A new screening programme has identified a series of small-molecule SIRT1 activators that are structurally unlike, and 1,000-fold more potent than, resveratrol, the well-known SIRT1 activator found in red wine. These new compounds improve metabolic function in animal models of diabetes and obesity, suggesting that they may have therapeutic potential in type 2 diabetes and insulin resistance.

Date: 2007
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DOI: 10.1038/nature06261

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