JCI InsightMilademetan is a Highly Potent MDM2 Inhibitor in Merkel Cell Carcinoma (MCC)

MDM2 is an important regulator of p53 and can be an effective therapeutic target in cancers. Pharmacological inhibition of MDM2 for stabilization of p53 has been of interest for several years and several MDM2 inhibitors targeting the MDM2-p53 interaction are currently in clinical trials. Approximately 80% of Merkel cell carcinoma (MCC) tumors have wild type p53 and could potentially respond to treatment with MDM2 inhibitors. In this study, milademetan showed a dose-dependent inhibition of tumor growth in MKL-1 xenograft and patient-derived xenograft models and is a potent MDM2 inhibitor in MCC.