Promoting degradation of the MDM2 oncogene for liposarcoma

INDICATION: Sarcoma

A pyrido-indole-based tool compound that triggers degradation of MDM2, an enzyme that suppresses p53 expression, could treat liposarcoma. In 10 human liposarcoma cell lines, the compound inhibited growth with IC₅₀ values of 0.2-3.2 μM. In xenograft mouse models of liposarcoma, including patient-derived xenograft (PDX) models, the MDM2 inhibitor reduced tumor growth. Ongoing work includes dynamic modeling, virtual screening and medicinal chemistry studies to identify compounds that reduce chromatin MDM2 load...