Inauhzin (INZ) is a small molecule SIRT1 inhibitor that effectively reactivates p53, promotes p53-dependent apoptosis of human cancer cells without causing apparently genotoxic stress.
Inauhzin (INZ) induced p53 levels as effectively as actinomycin D (ActD, 10 nM), did not apparently affect the interaction between either MDMX and p53, or MDM2 and MDMX, or MDM2 and p53.
Inauhzin inhibited cell growth in a p53-dependent fashion against human lung cancer H460, A549, H1299, colon cancer HCT116, HT29 (IC50=5-50 uM), induceed p53 level and activity as well as p53-dependent apoptosis.
Inauhzin (INZ) stabilizes p53 without either directly inhibiting MDM2-mediated ubiquitylation or causing genotoxicity.
Inauhzin (INZ) effectively inhibits SIRT1 deacetylase activity at 3 uM, directly binds to SIRT1 in vitro, induces p53 acetylation at lysine 382 at 2 uM in cells.
Inauhzin (INZ) induces p53 and p53-dependent apoptosis in vivo and suppresses the growth of human xenograft tumours.