Case Study: discovery of inhibitors of the MDM2-p53 protein-protein interaction.

The p53 protein, a tumor suppressor, is inactivated in many human cancers through mutations or by its interaction with an oncoprotein, MDM2. Blocking the MDM2-p53 protein-protein interaction has the effect of activating wild-type p53 and has been pursued as a novel anticancer strategy. Small-molecule inhibitors of the MDM2-p53 interaction have been discovered through various approaches, and a number of them have progressed into clinical trials for cancer treatment. Here, we describe the methods and techniques used in the discovery of small-molecule inhibitors of the MDM2-p53 interaction.