Chapter

Protein-Protein Interactions

Volume 8 of the series Topics in Medicinal Chemistry pp 57-79

Date:

Targeting the MDM2-p53 Protein-Protein Interaction for New Cancer Therapeutics

  • Shaomeng WangAffiliated withComprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan Email author 
  • , Yujun ZhaoAffiliated withComprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan
  • , Denzil BernardAffiliated withComprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan
  • , Angelo AguilarAffiliated withComprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan
  • , Sanjeev KumarAffiliated withComprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan

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Abstract

The p53 tumor suppressor protein is a transcriptional factor that plays a key role in regulation of several cellular processes, including the cell cycle, apoptosis, DNA repair, and angiogenesis. The murine double minute 2 (MDM2) protein is the primary cellular inhibitor of p53, functioning through direct interaction with p53. Design of non-peptide, small-molecule inhibitors that block the MDM2-p53 interaction has been sought as an attractive strategy to activate p53 for the treatment of cancer and other human diseases. In recent years, major advances have been made in the design of small-molecule inhibitors of the MDM2-p53 interaction in recent years, and several compounds have moved into advanced preclinical development or clinical trials. In this chapter, we will highlight these advances in the design and development of MDM2 inhibitors, and discuss lessons learned from these efforts.

Keywords

HDM2 Inhibitors MDM2 Protein-protein interactions