OM301

OM301 is a synthetic polypeptide therapeutic containing the p53 transactivation (p53TA) domain, developed by researchers at the City of Hope. Although originally designed to mimic the p53 interaction domain with MDM2 to prevent p53 degradation, subsequent research demonstrated that OM301 does not inhibit the p53-MDM2 interaction. Instead, it exerts its anti-tumor effects by directly interacting with c-Myc and members of the Bcl-2 family, including Bcl-2, Bcl-xL (Bcl2L1), Bclaf1, and Bcl2L13. This interaction induces mitochondrial dysfunction characterized by decreased mitochondrial membrane potential, increased mitochondrial superoxide production, and the induction of mitophagy and mitochondrial fission. OM301 has shown significant cytotoxic activity in multiple myeloma cell lines and animal models, regardless of their TP53 status, making it a potential therapeutic candidate for high-risk multiple myeloma.