Small molecule inhibitors of p53/MDM2 interaction

被引:37
作者
Fotouhi, N [1 ]
Graves, B [1 ]
机构
[1] Hoffmann La Roche Inc, Discovery Chem, Nutley, NJ 07110 USA
关键词
MDM2; P53; small molecule inhibitor; peptidic inhibitor; protein-protein interaction;
D O I
10.2174/1568026053507705
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页码:159 / 165
页数:7
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