MDM2 inhibitors: Targeting p53-MDM2 interaction to anti-cancer

P53 is a recognized tumor suppressor gene, which mainly depends on the activity of its transfer factor to realize effect. Mouse two-minute 2 (MDM2) an important inhibitor p53. When combined with MDM2, p53 will be reduced, and anti-cancer effect weakened. According mechanism between researchers focus inhibitors inhibit their binding. Through large number drug screening methods means, this article has found many new p53-MDM2 interaction, most are still in clinical research stage. Specifically, we classify drugs based different action mechanisms. Firstly, some combine MDM2 interaction. They Siremadlin (NVP-HDM201), RG7112, NVP-CGM09. While act p53, they rely induction signalling inhibition tumour cell proliferation wild-type lines, like MK-8242 KRT-232(AMG-232). What’s more, one inhibitor’s bases T cells APG-115. And last but not least, there also several that stable TP53, leading activation inducing cycle arrest apoptosis, Idasanutlin (RG7388) Milademetan (DS-3032/RAIN-32). Furthermore, studies finding monotherapy does deliver powerful therapeutic Various combination strategies being explored preclinically clinic. This talk about specific combinations: APG-115 immune checkpoint PD-1/PD-L1, BCL-2 inhibitors, anti-CD20 antibodies, last, alkylating agents.