IITZ-01

Treatment with IITZ-01 results in the vacuolated appearance of cells due to its specific accumulation in lysosomes. It deacidifies lysosomes and inhibits maturation of lysosomal enzymes leading to lysosomal dysfunction. IITZ-01 enhances autophagosome accumulation but inhibit autophagosomal degradation by impairing lysosomal function, finally resulting in the inhibition of autophagy. It also abolishes mitochondrial membrane potential and triggered apoptosis through the mitochondria-mediated pathway. In in-vitro screening assays, IITZ-01 shows negligible inhibition toward PI3K γ (IC50: 2.62 μM) and no significant inhibition at 10 μM against mTORC1. Immunoblotting experiment has revealed no significant decrease in p-AKT levels in breast cancer cells when treated with IITZ-01. IITZ-01 can trigger apoptosis via disrupting MMP and modulating Bcl-2 and IAP family proteins^[1].

MDA-MB-231 cells were treated with the designated concentrations (0.125-2 µM) of IITZ-01 and IITZ-02 for 24 h or 2 µM of IITZ-01 for specific time periods 3, 6, 12, 18, and 24 h. The protein expression levels of SQSTM1 were measured by western blotting experiment.

IITZ-01 displays potent antitumor action in vivo through autophagy inhibition and apoptosis induction in MDA-MB-231 breast cancer xenograft model^[1].