MDM2 Molecular Glue

Promotes cytosolic MDM2-NDUFS1 binding

A p53-independent MDM2 molecular glue that disrupts mitochondrial homeostasis via cytosolic MDM2-NDUFS1 binding, triggering the integrated stress response.

Wang, Rui · Gao, Yuan · Pan, Di · Guo, Yongjian · Wei, Libing Bin

Journal of Advanced Research 2026

Advantages

Binds NDUFS1, inhibits electron transport chain complex I formation

Disrupts mitochondrial homeostasis (altered membrane potential, superoxide, ATP generation, oxygen consumption rate)

Activates OMA1-DELE1 signaling axis

Induces integrated stress response-triggered apoptosis