Abstract
The discovery of the key negative regulator MDM2 (mouse double minute 2, also termed HDM2 for its human equivalent) provided a great opportunity to manipulate the levels of the tumor suppressor p53 in cancer cells. Activation of p53 in tumor cells by inhibiting the interaction of MDM2 with p53 has therefore been the focus of a large effort in drug discovery. The modulation of protein-protein interactions, however, has historically been very difficult to achieve owing to the large surface area of interaction. In this article, we review the recent accomplishments in this area and our quest for a clinically viable MDM2 inhibitor.
Keywords: mdm2, p53, small molecule inhibitor, peptidic inhibitor, protein-protein interaction
Current Topics in Medicinal Chemistry
Title: Small Molecule Inhibitors of p53/MDM2 Interaction
Volume: 5 Issue: 2
Author(s): Nader Fotouhi and Bradford Graves
Affiliation:
Keywords: mdm2, p53, small molecule inhibitor, peptidic inhibitor, protein-protein interaction
Abstract: The discovery of the key negative regulator MDM2 (mouse double minute 2, also termed HDM2 for its human equivalent) provided a great opportunity to manipulate the levels of the tumor suppressor p53 in cancer cells. Activation of p53 in tumor cells by inhibiting the interaction of MDM2 with p53 has therefore been the focus of a large effort in drug discovery. The modulation of protein-protein interactions, however, has historically been very difficult to achieve owing to the large surface area of interaction. In this article, we review the recent accomplishments in this area and our quest for a clinically viable MDM2 inhibitor.
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Cite this article as:
Fotouhi Nader and Graves Bradford, Small Molecule Inhibitors of p53/MDM2 Interaction, Current Topics in Medicinal Chemistry 2005; 5 (2) . https://dx.doi.org/10.2174/1568026053507705
DOI https://dx.doi.org/10.2174/1568026053507705 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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