Sphk1拮抗剂的研究进展  

Research Progress on Sphk1 Inhibitors

作　　者：杨皓然 杨新美 刘爱芹[1,2] 刘波[1,2] 姚庆强[1,2] YANG Hao-ran;YANG Xin-mei;LIU Ai-qin;LIU Bo;YAO Qing-qiang(School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan 250200,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, China;Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University (Shandong ProvincialQianfoshan Hospital), Jinan 250014, 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 [3]山东第一医科大学第一附属医院(山东省千佛山医院)药学部,山东济南250014

出　　处：《食品与药品》2019年第5期406-414,共9页Food and Drug

基　　金：山东省自然科学基金（No.ZR2017PH003）

摘　　要：鞘氨醇激酶1(sphingosine kinase 1,SphK1)是一种高度保守的ATP依赖的脂质激酶,在细胞内作为关键激酶调控神经酰胺(ceramide,Cer)、鞘氨醇(sphingosine,Sp)和鞘氨醇-1-磷酸(sphingosine1-phosphate,S1P)的代谢平衡。SphK1可促进Sp磷酸化生成S1P,通过SphK1-S1P-S1P受体(S1PR)信号通路调节细胞生长和凋亡。SphK1在多种肿瘤细胞中高表达,刺激细胞过度增殖,导致细胞恶性转化。SphK1是癌症治疗的理想靶标,设计、合成具有良好活性的SphK1拮抗剂是治疗癌症的重要策略。本文通过查阅近年文献,对SphK1的结构、功能及其在研拮抗剂的研究进展进行归纳综述,以冀为新型SphK1拮抗剂的研究开发提供参考。Sphingosine kinase 1 (SphK1) is a highly conserved ATP-dependent lipid kinase that is regarded as a key kinase regulating the metabolic balance of ceramide (Cer), sphingosine (Sp) and sphingosine 1-phosphate (S1P) in the cells. SphK1 can promote the phosphorylation of Sp to generate S1P and regulate cell growth and apoptosis through the SphK1-S1P-S1PR signaling pathway. SphK1 is highly expressed in a variety of tumor cells, stimulating excessive cell proliferation, leading to malignant transformation of cells. SphK1 is an ideal target for cancer treatment, design and synthesis of SphK1 inhibitors with good activity is an important strategy for the treatment of cancer. The research progress on structure and function of SphK1 and SphK1 inhibitors in recent years are reviewed in this paper, expecting to provide a reference for the research and development of new SphK1 inhibitors.

关 键 词：鞘氨醇激酶1 SphK1-S1P-S1PR信号通路 SphK1拮抗剂 

分 类 号：R963[医药卫生—微生物与生化药学]