Figure 1. Chemical structures of known and novel Sirtuin inhibitors.

Sirtinol (1) and EX-527 (2) are known Sirtuin inhibitors. 1 shows low potency and limited discrimination between Sirt1 and Sirt2. 2 is a potent Sirt1 inhibitor, shows much lower potency against Sirt2 and Sirt3, and has no effect on Sirt5, but data for other isoforms are lacking. The novel compounds 3 and 4 are potent Sirt2 inhibitors and show only weak effects on Sirt1, 3, 5, and 6 (see text).