蛋白-蛋白相互作用:抗肿瘤药物研发的新方向

被引：8

作者：

蒋永麟 ^{[1
,2
]}

姜正羽 ^{[1
,2
]}

尤启冬 ^{[1
,2
]}

机构：

[1] 中国药科大学江苏省药物分子设计与成药性优化重点实验室

[2] 中国药科大学药物化学教研室

来源：

中国新药杂志 | 2017年 / 26卷 / 10期

关键词：

蛋白-蛋白相互作用; 抗肿瘤; 小分子药物;

D O I：

暂无

中图分类号：

R979.1 [抗肿瘤、抗癌药物];

学科分类号：

100403 [营养与食品卫生学];

摘要：

肿瘤基因组学、靶向治疗和肿瘤生物学的研究进展明确了蛋白-蛋白相互作用(protein-protein interaction,PPI)在肿瘤发生发展中起着重要的作用,为抗肿瘤药物的研发提供了一个新的方向。然而,基于PPI的小分子药物研发面临着作用界面较大、结合口袋较浅等问题,使得基于PPI的药物开发极具挑战。近年来,PPI"热区"概念的提出,为基于PPI的小分子抑制剂的开发带来了新的思路。拟肽设计、片段筛选等药物发现策略的综合应用,丰富了PPI抑制剂开发的技术手段。由靶标验证(基于基因组学)、药物设计(基于PPI热区)以及临床研究(基于患者基因亚群)构成的三位一体开发模式逐步成形。可以预见,基于PPI的药物研发,将进一步促进肿瘤个体化医疗的发展。本文系统介绍了基于PPI发现抗肿瘤药物的方法,并对MDM2/p53,IAP,Bcl-2等热门靶标进行简要小结。

引用

页码：1119 / 1129

页数：11

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