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

Methods Mol Biol. 2015:1278:567-85. doi: 10.1007/978-1-4939-2425-7_38.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Humans
  • Protein Interaction Mapping / methods*
  • Protein Interaction Maps / drug effects*
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / metabolism*
  • Small Molecule Libraries / pharmacology
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / metabolism*


  • CNBP protein, human
  • RNA-Binding Proteins
  • Small Molecule Libraries
  • TP53 protein, human
  • Tumor Suppressor Protein p53