Protocol

Protein-Protein Interactions

Volume 1278 of the series Methods in Molecular Biology pp 567-585

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

  • Liu LiuAffiliated withComprehensive Cancer Center and Departments of Internal Medicine, University of MichiganPharmacology and Medicinal Chemistry, University of Michigan
  • , Denzil BernardAffiliated withComprehensive Cancer Center and Departments of Internal Medicine, University of MichiganPharmacology and Medicinal Chemistry, University of Michigan
  • , Shaomeng WangAffiliated withComprehensive Cancer Center and Departments of Internal Medicine, University of MichiganPharmacology and Medicinal Chemistry, University of Michigan Email author 

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Abstract

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