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Targeting the MDM2-p53 Protein-Protein Interaction for New Cancer Therapy: Progress and Challenges

Shaomeng Wang1, Yujun Zhao1, Angelo Aguilar1

  • 1University of Michigan Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109.

Cold Spring Harbor Perspectives in Medicine
|March 9, 2017
PubMed

Insights

Small-molecule inhibitors targeting the MDM2-p53 interaction are emerging as promising cancer treatments. These drugs reactivate the p53 tumor suppressor, showing potential in clinical trials for various cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • MDM2 protein inhibits the tumor suppressor p53.
  • Blocking the MDM2-p53 interaction can restore p53's anti-cancer function.
  • This strategy is particularly relevant for cancers with wild-type p53.

Purpose of the Study:

  • To review the design and development of small-molecule MDM2 inhibitors.
  • To discuss early clinical data of these novel anticancer agents.
  • To identify future challenges in the clinical development of MDM2 inhibitors.

Main Methods:

  • Review of scientific literature on MDM2 inhibitors.
  • Analysis of drug design strategies for targeting protein-protein interactions.
  • Examination of early-phase clinical trial data.

Main Results:

  • Numerous potent, nonpeptide small-molecule MDM2 inhibitors have been developed.
  • Seven such inhibitors have progressed to human clinical trials.
  • Early clinical data suggest therapeutic potential for these compounds.

Conclusions:

  • Small-molecule MDM2 inhibitors represent a promising therapeutic strategy for cancer.
  • Continued research and development are crucial for overcoming clinical challenges.
  • Successful development could lead to new treatments for wild-type p53 cancers.

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