鞘氨醇激酶1抑制剂的研究进展  

Research progress of sphingosine kinase 1 inhibitors

作　　者：杨倩[1] 汪小涧 YANG Qian;WANG Xiaojian(Patent Examination Cooperation(Beijing)Center of the Patent Office,China National Intellectual Property Administration,Beijing 100160;State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100050,China)

机构地区：[1]国家知识产权局专利局专利审查协作北京中心,北京100160 [2]中国医学科学院、北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《中国药科大学学报》2021年第6期759-768,共10页Journal of China Pharmaceutical University

摘　　要：鞘氨醇激酶1(SphK1)是调控细胞膜脂质微环境的重要蛋白,在神经酰胺,鞘氨醇和鞘氨醇-1-磷酸的动态平衡中发挥重要作用。SphK1的过度表达与肿瘤的发生,发展和迁移过程以及产生耐药性有着密切的联系。SphK1抑制剂可以诱导多种肿瘤细胞凋亡,并且可以逆转肿瘤耐药性,具有良好的药物开发前景。本文综述了SphK1的结构生物学以及SphK1抑制剂的结构类型和构效关系研究进展。Sphingosine kinase 1(SphK1)is an important protein that regulates the lipid microenvironment of cell membranes,and plays an important role in the dynamic equilibrium of ceramide,sphingosine and sphingo⁃sine-1-phosphate.The overexpression of SphK1 is closely related to the occurrence,development and migration of tumors as well as the generation of drug resistance.SphK1 inhibitors can induce apoptosis of various tumor cells and reverse drug resistance,which has a good prospect for drug development.In this article,the structural biology of SphK1,the structural types and structure-activity relationships of SphK1 inhibitors are reviewed.

关 键 词：鞘氨醇激酶-1 抑制剂 抗肿瘤 结构类型 构效关系 进展 

分 类 号：R979.1[医药卫生—药品]