Targeting the p53-MDM2 interaction to treat cancer

Br J Cancer. 2004 Oct 18;91(8):1415-9. doi: 10.1038/sj.bjc.6602164.


The tumour suppressor p53 is a transcription factor with powerful antitumour activity that is controlled by its negative regulator MDM2 (mouse double minute 2, also termed HDM2 in humans) through a feedback mechanism. MDM2, which is overproduced in many tumours, binds p53 and inhibits its function by modulating its transcriptional activity and stability. Activation of p53 in tumour cells by inhibiting its physical interaction with MDM2 has been in the focus of cancer drug discovery. However, development of nonpeptidic MDM2 antagonists turned out to be challenging. Recently, the first potent and selective small-molecule antagonists of MDM2, the Nutlins, have been identified. Studies with Nutlins provided in vitro and in vivo proof-of-principle for targeting p53-MDM2 interaction for cancer therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Nuclear Proteins / metabolism*
  • Protein Binding / drug effects
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-mdm2
  • Tumor Suppressor Protein p53 / metabolism*


  • Antineoplastic Agents
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2