Case Study: Discovery of Inhibitors of the MDM2–p53 Protein-Protein Interaction

Part of the Methods in Molecular Biology book series (MIMB, volume 1278)


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.

Key words

p53 MDM2 Protein-protein interaction Cancer therapy High-throughput screening Virtual screening 


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Comprehensive Cancer Center and Departments of Internal MedicineUniversity of MichiganAnn ArborUSA
  2. 2.Pharmacology and Medicinal ChemistryUniversity of MichiganAnn ArborUSA

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