Abstract
The potentiation of p53 activity through inhibition of its negative regulator MDM2 is an attractive strategy for anticancer therapy. Much progress has been made in the last decade in a diverse range of areas related to p53 and MDM2. This review focuses on the recent progress in developing small-molecule inhibitors of the MDM2 protein by covering the following approaches that inhibit the function of the p53–MDM2 axis: (1) direct binding to MDM2, (2) direct binding to p53, (3) targeted degradation of MDM2 by the PROTAC approach, and (4) inhibition of MDM2/MDM4 interaction. Given the importance of p53 in cancer development, we hope that research in this area will lead to anticancer drugs in the not too distant future.
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