Inauhzin

Inauhzin is a dual SirT1/IMPDH2 inhibitor, and acts as an activator p53, used in the research of cancer. IC50 & Target: SirT1, IMPDH2, MDM-2/p53^[3] In Vitro: Inauhzin (10 µM) induces p53 levels as effectively as actinomycin D (10 nM), and mediates p53-dependent cytotoxicity through its specific functional groups in human lung carcinoma H460 cells. Inauhzin (2 µM) induces p53 level and activity as well as p53-dependent apoptosis. Inauhzin also stabilizes p53 and inhibits its ubiquitylation. Inauhzin induces acetylation of p53 in H460 cells, but not tubulin, which is affected by knockdown of SIRT1^[1]. Inauhzin (0-2 µM) significantly enhances the expression level and activity of p53 in HCT116^p53+/+ cells and enhances the expression level and activity of p53 in H460 cells in a dose-dependent manner. Inauhzin and Nutlin-3 demonstrate synergistic cytotoxicity in the Nutlin-3 low-sensitive cells. Inauhzin and Nutlin-3 synergistically induce p53-dependent apoptosis^[2]. Inauhzin targets both SirT1 and IMP dehydrogenase 2 (IMPDH2), and acts as a potent p53 activator^[3]. In Vivo: Inauhzin (30 mg/kg, i.p.) effectively induces apoptosis and suppresses tumour growth of H460 xenograft harbouring p53^[1]. Inauhzin (30 mg/kg, i.p.) reduces the HCT116 tumor volume by appr 70%. Inauhzin (15 mg/kg) in combination with 150 mg/kg of Nutlin-3 demonstrates a significant synergy on p53 induction, apoptosis and tumor suppression of HCT116^p53+/+ xenografts^[2].