MDM4 and cancer: This proof-of-concept study outlines DRx-098D-R’s ability to (1) directly bind MDM2 and MDMX, (2) disrupt intracellular MDM2 homo- and heterodimerization, (3) inhibit MDM2 E3 ligase activity, and (4) promote cancer cell death across a broad spectrum of TP53 WT and MT human cancer cell models.