SphK1抑制剂的合成研究进展  

Research progress on synthesis of SphK1 inhibitors

作　　者：杨皓然 柴会宁 刘爱芹[1,2] 郑重飞[1,2] 刘波 姚庆强[1,2] YANG Haoran;CHAI Huining;LIU Aiqin;ZHENG Zhongfei;LIU Bo;YAO Qingqiang(School of Medicine and Life Sciences,University of Jinan-Shandong Academy of Medical Sciences,Jinan 250200,Shandong,China;Institute of Materia Medica,Shandong Academy of Medical Sciences,Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory of Rare and Uncommon Diseases of Shandong Province,Jinan 250062,Shandong,China)

机构地区：[1]济南大学山东省医学科学院医学与生命科学学院,山东济南250200 [2]山东省医学科学院药物研究所,国家卫生部生物技术药物重点实验室,山东省罕少见病重点实验室,山东济南250062

出　　处：《化学研究》2019年第4期411-428,共18页Chemical Research

基　　金：山东省自然科学基金(ZR2017PH003);山东省医学科学院医药卫生科技创新工程

摘　　要：鞘氨醇激酶1(Sphingosine kinase 1, SphK1)是一种ATP依赖的脂质激酶,作为关键酶催化鞘氨醇(Sphingosine, Sp)向鞘氨醇-1-磷酸(Sphingosine 1-phosphate, S1P)转化. S1P是细胞内一种重要的信号分子,通过激活细胞内多种信号通路调控细胞的存活或死亡.细胞内SphK1的过度表达,会使胞内S1P水平升高,刺激细胞过度增殖,导致细胞恶性转化,诱发癌变.因此,SphK1可视为癌症治疗的靶标,设计合成靶向SphK1的抑制剂,是治疗癌症的有效方法.迄今为止,已有多种SphK1抑制剂被陆续报道.本文通过对相关合成工作进行归纳综述,期望为新型SphK1抑制剂的开发提供参考.Sphingosine kinase 1 (SphK1) is a highly conserved lipid kinase which was considered as a key enzyme to catalyzes Sphingosine (Sp) to Sphingosine 1-phosphate (S1P). S1P is an important signaling molecule in cells that regulates cell survival or death by activating multiple signaling pathways. The overexpression of SphK1 will increase the intracellular S1P level, stimulate the cells to proliferate excessively, cause malig-nant transformation of the cells, and induce canceration. Therefore, SphK1 can be regarded as a target for cancer treatment. Designing and synthesizing inhibitors targeting SphK1 is an effective method for treating cancer. Up to now, many SphK1 inhibitors have been reported in succession. Herein, we summarize the relevant synthesis work, expecting to provide reference for the development of novel SphK1 inhibitors.

关 键 词：鞘氨醇激酶1抑制剂 合成 抗肿瘤 

分 类 号：R914.5[医药卫生—药物化学]