Cyclic peptide-based potent and selective SIRT1/2 dual inhibitors harboring Nε-thioacetyl-lysine

N-terminus-to-side chain cyclic tripeptides (4, 5, 12) harboring the catalytic mechanism-based SIRT1/2/3 inhibitory warhead Nε-thioacetyl-lysine at their central positions were found to exhibit strong and selective (versus SIRT3/5/6) dual SIRT1/2 inhibition.125