P53-MDM2 抑制剂。
P53 mdm2 inhibitors.
机构信息
University of Pittsburgh, Department of Pharmaceutical Sciences, Pittsburgh, PA 15261, USA.
出版信息
Curr Pharm Des. 2012;18(30):4668-78. doi: 10.2174/138161212802651580.
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.
摘要
p53 与其负调控因子 MDM2 之间的蛋白-蛋白相互作用（PPI）是参与预防癌症发生的最重要和研究最深入的 PPI 之一。p53 和 MDM2 之间的相互作用基于构象，在多个层面受到严格调控。由于在埃分辨率水平上的结构见解，人们对分子与 MDM2 结合并成功抑制 p53/MDM2 相互作用所需的结构要求有了合理的理解。本综述总结了不同公开的小分子抑制 MDM2 的结合特性，其中包含共晶结构。详细描述了这些化合物及其衍生物的合成方法。
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