Inauhzin is a cell-permeable, SIRT1 inhibitor (IC50 = 0.7-2 μM) that reactivates p53 by inhibiting SIRT1 deacetylation activity. It binds directly to SIRT1 and does not affect SIRT2, SIRT3, or HDAC8. Inauhzin has been shown to inhibit cell proliferation by inducing p53-dependent apoptosis in various human cancer cells (IC50s = 5.4, 51.9, 3.2, 33.9, and 85.4 μM for H460, H1299, A549, HT-29, and WI38 cells, respectively), as well as in xenograft tumors derived from H460 cells. It has also been shown to activate p53 synergistically with the Mdm2 inhibitor nutlin-3 , sensitizing cancer cells to cisplatin and doxorubicin .
