FIG. 1.

EX-527 is a potent inhibitor of SIRT1 that also inhibits Sir2-dependent silencing in yeast. (A) Structure of EX-527. (B) EX-527 inhibits deacetylase activity of purified human SIRT1. Deacetylase activity of GST-SIRT1 in the presence of increasing concentrations of EX-527 was measured by the Fluor de Lys assay. Samples were assayed in triplicate and analyzed using Prism (Graphpad Software, Inc.). (C) The active optical isomer of EX-527, EX-243, and not the inactive optical isomer, EX-242, inhibits Sir2-dependent silencing in yeast. A yeast strain constructed with a URA3 gene inserted near a telomere was grown in the presence of compounds with or without 5-FOA. Growth was measured by light scattering at 600 nm.