Hu Chun-Qi, Hu Yong-Zhou
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Curr Med Chem. 2008;15(17):1720-30. doi: 10.2174/092986708784872375.
Recent researches have discovered that MDM2 (murine double minute 2, or HDM2 for the human congener) protein is the main negative regulator of p53, which is an attractive therapeutic target in oncology because its tumor-suppressor activity which can be stimulated to eradicate tumor cells. Inhibiting the p53-MDM2 interaction is a promising approach for activating p53, because this association is well characterized at the structural and biological levels. A number of drug screening approaches and technologies have been used to identity novel inhibitors of the p53-MDM2 interaction. This review will detail the development history of MDM2 protein and the p53-MDM2 interaction, the major classes of novel small-molecular p53-MDM2 binding inhibitors, key medicinal action with the protein-protein interaction and in vitro or in vivo biological activities.
最近的研究发现，MDM2（小鼠双微体2，人类同源物为HDM2）蛋白是p53的主要负调控因子，p53是肿瘤学中一个有吸引力的治疗靶点，因为其肿瘤抑制活性可被激活以根除肿瘤细胞。抑制p53-MDM2相互作用是激活p53的一种有前景的方法，因为这种关联在结构和生物学水平上已得到充分表征。许多药物筛选方法和技术已被用于鉴定p53-MDM2相互作用的新型抑制剂。本综述将详细介绍MDM2蛋白和p53-MDM2相互作用的发展历史、新型小分子p53-MDM2结合抑制剂的主要类别、与蛋白质-蛋白质相互作用相关的关键药用作用以及体外或体内生物学活性。
