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SirReal2 is a potent and selective Sirt2 inhibitor with IC₅₀  ~140 nM, has minimal effect on Sirt1 and Sirt3-6. It occupies the extended C-site and induces a major rearrangement of Sirt2’s active site, so it selectively inhibits Sirt2 and functions as a molecular wedge to lock Sirt2 in an open conformation. SirReal2 can increase tubulin hyperacetylation in HeLa cells and induces destabilization of the checkpoint protein BubR1. It could be a useful chemical tool for sirtuin biology.

• 1. Rumpf T, et al. Selective Sirt2 inhibition by ligand-induced rearrangement of the active site. (2015) Nat Commun. 6:6263.