Navigating the p53‐MDM2 Landscape: Molecular Insights and Therapeutic Strategies

ABSTRACT MDM2 is categorised as a critical oncogenic regulator that negatively controls the tumour suppressor p53, making it an important target for cancer therapy. With the aim of restoring the p53 activity through disrupting MDM2‐p53 interaction, several strategies, including small‐molecule inhibitors, have been developed, thereby promoting cancer cell apoptosis. Numerous chemical scaffolds were widely employed in designing and synthesising MDM2 inhibitors. This review summarises the advances in structure‐based drug design and virtual screening approaches that allowed the generation of potent inhibitors with improved binding affinity, selectivity and pharmacokinetic profiles. We also discuss limitations such as chemical stability and innovative approaches such as targeted MDM2 degradation.