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Methods Mol Biol. 2015;1278:567-85. doi: 10.1007/978-1-4939-2425-7_38.

Case Study: discovery of inhibitors of the MDM2-p53 protein-protein interaction.

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


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.

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