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Updated: May 3, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
The p53-MDM2/MDMX axis - A chemotype perspective
Kareem Khoury1, Grzegorz M Popowicz2, Tad A Holak2
1University of Pittsburgh, Department of Pharmaceutical Science, Drug Discovery Institute, Pittsburgh, PA, USA.
Abstract:
The protein-protein interaction (PPI) of the tumor suppressor p53 and its negative regulator MDM2 consists of the most intense studied PPI with a group of small molecular weight antagonists described and many more disclosed in patent literature. Due to the Å-level structural insight into p53 interaction with MDM2 there is a reasonable understanding of the requirements of the molecules to bind. In contrast and despite the very close homology and 3-D similarity no potent MDMX antagonist has been disclosed up to date. The current review summarizes the different disclosed chemotypes for MDM2 including a discussion of the cocrystal structures. Structures and approaches to reconstitute functional p53 from mutated p53 are presented. Finally new screening methods and recent biotech deals based on p53 are discussed.
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