摘要
目的了解磷脂酰肌醇-4-磷酸酯(PI4P)代谢酶及抑制剂的研究进展,为PI4P信号通路相关靶点药物的研发提供参考。方法对作用于PI4P的6种代谢酶的基本情况、对疾病的影响及典型抑制剂的应用进行总结,并分析现有研究中仍待解决的问题,探讨PI4P代谢酶及抑制剂作为相关疾病治疗靶点的可能性。结果PI4P是一种膜甘油磷脂,由磷脂酰肌醇(PtdIns)4位羟基磷酸化生成;是高尔基体膜的关键功能成分,在囊泡运输和信号传导中不可或缺。尽管对PI4P的生理作用已有深入研究,但对PI4P的代谢调控知之甚少。PI4P代谢酶在肿瘤方面的研究较多,发现磷脂酰肌醇-3-激酶(PI3K)高表达与多种肿瘤的恶化有关,目前已有4种PI3K抑制剂作为抗肿瘤药物被批准上市。结论PI4P代谢酶除了能调控肿瘤的进展外,还参与炎症激活、病毒及疟疾感染、阿尔茨海默病等临床常见疾病的发生与发展,但相关研究多停留在基础实验阶段,相关抑制剂可能是治疗上述疾病的有效方法。
ObjectiveTo understand the research progress of phosphatidylinositol-4-phosphate(PI4P)metabolic enzymes andtheir inhibitors,and to provide a reference for the research and development of targeted drugs related to the PI4P signalingpathway.MethodsThe basic information,the effects on the diseases of six metabolic enzymes regulating PI4P and the applicationof typical inhibitors were summarized.The problems still to be solved in the current research were analyzed.The possibility of PI4Pmetabolic enzymes and their inhibitors as therapeutic targets for related diseases were investigated.ResultsPI4P was a membraneglycerophospholipid,which was formed by the phosphorylation of the 4-hydroxyl of phosphatidylinositol(PtdIns).PI4P was a keyfunctional component of the Golgi apparatus membrane,which was indispensable in the vesicle transport and signaling transduction.Although the physiological role of PI4P had been deeply studied,little was known about its metabolic regulation.There were manystudies on the PI4P metabolic enzymes in the tumors,among which the high expression of phosphatidylinositol-3-kinase(PI3K)was found to be associated with the deterioration of various tumours.At present,four PI3K inhibitors had been approved formarketing as the anti-tumor drugs.ConclusionIn addition to regulating the progression of tumors,PI4P metabolic enzymes also involved in the occurrence and development of common clinical diseases such as inflammatory activation,virus and malariainfection,Alzheimer’s disease.However,most of the related studies remain in the basic experimental stage,and related inhibitors maybe the effective treatment for these diseases.
作者
李艳平
李晨
LI Yanping;LI Chen(Department of Pharmacy,Daping Hospital,Army Medical University,Chongqing,China 400042)
出处
《中国药业》
CAS
2022年第19期117-123,共7页
China Pharmaceuticals
基金
重庆市首批临床药学重点专科建设项目[渝卫办发[2020]68号]。
