alpha-Mangostin (Mangostin) is a natural xanthonoid, a type of organic compound isolated from various parts of the mangosteen tree.

Alpha-mangostin exhibits a selective inhibitory effect on IDH1-R132H, but not on IDH1. Alpha-mangostin competitively inhibits the binding of alpha-mangostin (α-KG) to IDH1-R132H. The structure–relationship study reveals that alpha-mangostin exhibits the strongest core inhibitor structure. Alpha-mangostin selectively promotes demethylation of 5-methylcytosine (5mC) and histone H3 trimethylated lysine residues in IDH1 (+/R132H) MCF10A cells[1]. Cell proliferation significantly decreases in a dose-dependent manner in the cells treated with alpha-mangostin. Alpha-mangostin also increases the levels of Bax (pro-apoptotic), cleaved caspase-3, cleaved caspase-9 and cleaved-poly(ADP-ribose) polymerase (PARP)[2]. Alpha-mangostin significantly inhibits light-induced degeneration of photoreceptors and 200 μM Water2-induced apoptosis of RPE cells. 200 μM Water2-induced generation of reactive oxygen species (ROS) and light-induced generation of malondialdehyde (MDA) are suppressed by alpha-mangostin[3].

Alpha-mangostin mitigates the risk of liver fibrosis by diminishing p53 expression relative to TAA_DMSO treatment. Moreover, following α-mangostin administration, serum concentrations of liver enzymes AST and ALT are reduced in comparison to treatment with DMSO alone[4].

IDH1+/+ and IDH1