靶向p53-MDM2的喹啉类抗肿瘤小分子化合物的虚拟筛选

Virtual Screening of Quinoline Antitumor Small Molecular Compounds Targeting the p53-MDM2 Interaction

摘要: p53能诱导细胞凋亡，抑制肿瘤的发生发展。MDM2是p53最重要的负调控因子，能诱导p53的泛素化降解，抑制p53的功能。因此，针对p53-MDM2设计小分子靶向抑制剂是开发新型抗肿瘤药物的一种极具前景的策略。喹啉类化合物及其衍生物是具有抗肿瘤活性的小分子药物的重要来源。本研究以p53-MDM2为药物靶点，对喹啉类化合物库进行了基于药效团和分子对接的虚拟筛选，最终获得了具有潜在的靶向p53-MDM2抗肿瘤的小分子化合物Compound 6和Compound 9。本研究为靶向抗癌药物研发提供了一种筛选方法，并为进一步开发针对p53-MDM2的小分子靶向药奠定了基础。

Abstract: p53 can induce cell apoptosis and inhibit tumor occurrence and development. MDM2 is the most important negative regulator of p53, which can induce the ubiquity nation and degradation of p53, and inhibit its function. Therefore, designing small molecular inhibitors against p53-MDM2 is a promising strategy for the development of novel antitumor drugs. Quino line and its derivatives are important sources of small molecular drugs with potential antitumor activities. In this work, using the p53-MDM2 as the target, we performed virtual screening on the quino line compound library based on pharmacophore modeling and molecular docking, and finally obtained Compound 6 and Compound 9 which have potential antitumor activities against p53-MDM2.This work provides a screening method for the discovery of targeted antitumor drugs, and lays the foundation for further development of small molecular inhibitors against p53-MDM2.