Thiomyristoyl

Thiomyristoyl is a highly selective and potent SIRT2 inhibitor with IC50 of 28 nM, displays no significant activity against SIRT1/3/5/6/7 (Ic50>100 uM) ; promotes c-Myc ubiquitination and degradation, exhibits broad anticancer effect in various human cancer cells while having limited effects on non-cancerous cells; demonstrates in vivo effect in mouse models of breast cancer. (In Vitro) :Thiomyristoyl (TM) is a potent SIRT2-specific inhibitor with broad anticancer activity but little effect on non-cancerous cells. SIRT2-inhibition promotes c-Myc ubiquitination and degradation, suggesting the therapeutic potential of TM to target certain c-Myc-driven cancers. TM could inhibit SIRT2 with an IC50 of 28 nM, but inhibits SIRT1 with an IC50 value of 98 μM and does not inhibit SIRT3 even at 200 μM. TM inhibits three human breast cancer cell lines, MCF-7, MDA-MB-468, and MDA-MB-231. (In Vivo) :TM inhibits tumor growth in mouse models of breast cancer. TM does not cause significant toxicity in mice and no significant weight loss is observed in TM-treated mice. S5H, the acetyl-a-tubulin level is moderately but statistically significantly increased in tumors from TM-treated mice compared with those from vehicle-treated mice, suggesting that TM indeed inhibits SIRT2 in vivo.