Abstract
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.
Current Pharmaceutical Design
Title:P53 Mdm2 Inhibitors
Volume: 18 Issue: 30
Author(s): Kareem Khoury and Alex Domling
Affiliation:
Keywords: p53, MDM2, HDM2, protein protein interactions, small molecule inhibitors, negative regulator, cancer, Angstrom level, p53/MDM2 interaction, derivatives.
Abstract: 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.
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Cite this article as:
Khoury Kareem and Domling Alex, P53 Mdm2 Inhibitors, Current Pharmaceutical Design 2012; 18 (30) . https://dx.doi.org/10.2174/138161212802651580
DOI https://dx.doi.org/10.2174/138161212802651580 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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