SIRT2 and breast cancer: Systematic structure–activity relationship (SAR) studies of SIRT2 inhibitors with 2-((4,6-dimethylpyrimidin-2-yl)thio)-N-phenylacetamide core scaffold led to the discovery of more potent inhibitors such as 7 and 8.30,31 Crystal structure revealed the specific hydrophobic binding features of 8 to SIRT2 (Fig. 2C), which likely mimics the binding of long-chain acyl-lysine substrates.27 Biological experiments have shown that compound 7 has obvious inhibitory effects on breast cancer cell MCF-7 and can increase the acetylation level of α-tubulin in a dose-dependent manner.