MEL23 is an MDM2E3 ligase inhibitor that prevents the E3 ligase activity of the MDM2-MDMX complex. It inhibits the ubiquitination of Mdm2 and p53 in cells, reducing the viability of wild-type p53 cells. Additionally, MEL23 stabilizes MDM2 through a mechanism independent of p53 transcription.

MEL23 enhances the luminescence of Mdm2 (wt)-luciferase cells with an EC50 of 2.7 μg/mL [1]. MEL23 (3.16-100 μM; 48 hours) induces p53-dependent cell death [1]. At concentrations of 2.5-5 μg/mL for 48 hours, MEL23 increases the sub-G1 cell population and causes a slight G2 cell cycle arrest in HT-1080 cells [1]. After 6 hours at 5 μg/mL, it raises the levels of Mdm2, p53, and MdmX, thereby activating p53 [1]. The transcription of p53 target genes such as Mdm2, p21, puma, and bax is elevated when exposed to MEL23 at 5 μg/mL for 24-48 hours [1]. In parental HT-1080 cells, MEL23 inhibits Erastin-induced cell death and significantly reduces the extent of ferroptosis [2].