Definition

A small molecule protein and selective degrader of the oncoprotein murine double minute 2 (MDM2), with potential immunomodulating and antineoplastic activities. Upon administration, MDM2 degrader KT-253 binds to MDM2 and the E3 (ubiquitin) ligase and targets MDM2 for ubiquitination. This induces proteasome-mediated degradation of MDM2 and prevents its binding to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this MDM2-p53 interaction, the transcriptional activity of p53 is restored and leads to the stabilization of p53 levels. This leads to p53-mediated induction of tumor cell apoptosis. MDM2, a zinc finger protein and a negative regulator of the p53 pathway, is overexpressed in cancer cells; it plays a key role in cancer cell proliferation and survival.