FIGURE 2. In vitro characterization of activators of human SIRT1.
From the following article:
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 & Christoph H. Westphal
Nature 450, 712-716(29 November 2007)
doi:10.1038/nature06261
a, The effect of SIRT1 activators on peptide substrate Km. b, Calorimetric titrations of SIRT1-C–peptide substrate complex with the activator SRT1460. Top panel: heat of binding SRT1460 to enzyme–peptide complex. Bottom panel: integrated fit with a one-site binding model. c, Isobologram analysis of resveratrol versus SRT1720 and SRT1720 versus SRT1460. The experimental data are best fit to the theoretical line of additivity (dashed line). d, SIRT1 N-terminal truncations define the allosteric compound binding site. The ability of resveratrol and SRT1720 to activate SIRT1 was examined against a series of N-terminal deletions in the mass spectrometry assay.
