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

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Book cover Protein-Protein Interactions

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 8))

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.

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Acknowledgements

Funding from the National Cancer Institute/National Institutes of Health, the Prostate Cancer Foundation, the Leukemia and Lymphoma Society, Ascenta Therapeutics and Sanofi is greatly appreciated.

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Authors and Affiliations

  1. Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA

    Shaomeng Wang, Yujun Zhao, Denzil Bernard, Angelo Aguilar & Sanjeev Kumar

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  1. Shaomeng Wang
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  2. Yujun Zhao
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Correspondence to Shaomeng Wang .

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  1. , Global Pharmaceutical R & D, Abbott Laboratories, Dept R4N6 / Bldg AP10-3, Abbott Park Rd 100, Abbott Park, 60064, Illinois, USA

    Michael D. Wendt

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Wang, S., Zhao, Y., Bernard, D., Aguilar, A., Kumar, S. (2012). Targeting the MDM2-p53 Protein-Protein Interaction for New Cancer Therapeutics. In: Wendt, M. (eds) Protein-Protein Interactions. Topics in Medicinal Chemistry, vol 8. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28965-1_2

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