MMRi62

MMRi62 is a small molecule quinolinol that acts as an inhibitor of the MDM2-MDM4 E3 ligase complex. Originally identified through a high-throughput screen for MDM2-MDM4 inhibitors, MMRi62 distinguishes itself by promoting the degradation of MDM4 (also known as MDMX) and inducing apoptosis in a p53-independent manner. This mechanism allows it to remain effective in cancer cells where p53 is mutated or deficient, a common limitation of traditional MDM2 inhibitors. Research has demonstrated its potency in solid tumors, particularly melanoma, where it can overcome resistance to BRAF inhibitors. Chemical biology profiling of its derivatives suggests that MMRi62-like quinolinols function as multi-targeting covalent inhibitors that disrupt various cellular processes, including carbon metabolism, RNA metabolism, and protein translation.