The protein-protein interaction (PPI) between p53 and its negative regulator MDM2 comprises one of the most important and
intensely studied PPI's involved in preventing the initiation of cancer. The interaction between p53 and MDM2 is conformation-based
and is tightly regulated on multiple levels. Due to the Angstrom level structural insight there is a reasonable understanding of the structural
requirements needed for a molecule to bind to MDM2 and successfully inhibit the p53/MDM2 interaction. The current review
summarizes the binding characteristics of the different disclosed small molecules for inhibition of MDM2 with a co-crystal structure.
Synthetic access to these compounds as well as their derivatives are described in detail.
Keywords: p53, MDM2, HDM2, protein protein interactions, small molecule inhibitors, negative regulator, cancer, Angstrom level, p53/MDM2 interaction, derivatives.
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