SIRT1/2 Inhibitor IV (cannabinol) is a small-molecule inhibitor of SIRT1 and SIRT2 with IC50 values of 56 μM and 59 μM, respectively.

SIRT1/2 Inhibitor IV is a cell-permeable SIRT1 and SIRT2 inhibitor. SIRT1/2 Inhibitor IV inhibited human SIRT1 and SIRT2 NAD-dependent deacetylase activity with IC50 values of 56 and 59 μmol/L, respectively. In the NCI H460 lung cancer cell line, combined inhibition of SIRT2 and HDAC6 with SIRT1/2 Inhibitor IV and trichostatin A resulted in hyperacetylation of tubulin. SIRT1/2 Inhibitor IV also increased acetylation of p53. In p53-positive lung cancer cell line NCI H460, SIRT1/2 Inhibitor IV mediated inhibition of SIRT1 sensitized cells to etoposide in a p53-independent manner [1].

In a mouse xenograft model, SIRT1/2 Inhibitor IV (100 mg/kg) administered i.v. into the tail vein or i.p. daily for 2 weeks (five injections per week) reduced tumor growth [1]. In mice pre-treated with cannabinol for 2 hours and then exposed to 6% oxygen for 6 hours, cannabinol significantly reduced EPO mRNA in the kidney and the liver [2].