胰高血糖素样肽-1类似物研发进展  

Progress in Research and Development of Glucagon-Like Peptide-1 Analogues

作　　者：冉雨叶 郑珩[1] RAN Yuye;ZHENG Heng(School of Life Science and Technology,China Pharmaceutical University,Nanjing,Jiangsu,China 211198)

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京211198

出　　处：《中国药业》2024年第8期128-128,I0001-I0008,共9页China Pharmaceuticals

基　　金：国家自然科学基金[82073767]。

摘　　要：目的总结胰高血糖素样肽-1(GLP-1)类似物的研发进展。方法检索PubMed和Web of Science数据库自建库起至2024年2月20日的GLP-1类似物相关文献,从研发概况、单分子多靶点GLP-1受体激动剂(GLP-1RA)、除治疗糖尿病外的其他适应证及其药物研发新趋势方面,总结GLP-1类似物的研发进展。结果与结论GLP-1类似物的研发经历了从短效到长效,从注射剂到口服剂,并扩展到多靶点治疗的过程。目前,多靶点GLP-1RA包括GLP-1R/葡萄糖依赖性促胰岛素释放多肽受体、GLP-1R/胰高血糖素受体(GCGR)、GLP-1R/GLP-2R、GLP-1R/胰淀素3受体(AMY3R)、GLP-1R/成纤维细胞生长因子21受体(FGF-21R)等双靶点激动剂,以及GLPR/GLP-1R/GCGR、GLP-1R/GCGR/FGF-21R等三靶点激动剂。GLP-1类似物展现了在2型糖尿病、超重、肥胖症、心血管疾病、多囊卵巢综合征、非酒精性脂肪性肝炎、慢性肾脏病等疾病治疗的巨大潜力,疗效优于单靶点的双靶点和三靶点GLP-1RA是近年来研发的重点。GLP-1类似物的重组腺相关病毒载体基因治疗为研发新趋势,其现阶段存在的安全性、依从性等问题和可供参考的解决方法也一并被提出。Objective To summarize the progress of research and development(R&D)for glucagon-like peptide-1(GLP-1)analogues.Methods The literature related to GLP-1 analogues in the PubMed and Web of Science from the inception of these databases to February 20,2024 were searched to summarize the R&D progress of GLP-1 analogues from the R&D overview,mono-molecule multi-target GLP-1 receptor agonists(GLP-1RAs),other indications except diabetes mellitus and new trends in R&D.Results and Conclusion GLP-1 analogues has evolved from short-acting to long-acting formulations,from injection to oral medication,and developed to the drugs through multi-target treatment.At present,multi-target GLP-1RAs include dual-target agonists[GLP-1R/glucose-dependent insulinotropic polypeptide receptor,GLP-1R/glucagon receptor(GCGR),GLP-1R/GLP-2R,GLP-1R/amylin 3 receptor(AMY3R),GLP-1R/fibroblast growth factor 21 receptor(FGF-21R)]and triple-target agonists(GLPR/GLP-1R/GCGR,GLP-1R/GCGR/FGF-21R).GLP-1 analogues show great potential in the treatment of diabetes mellitus type 2,overweight,obesity,cardiovascular disease,polycystic ovary syndrome,non-alcoholic steatohepatitis and chronic kidney disease.The dual-target and triple-target GLP-1RAs,which are more effective than single-target GLP-1RAs,have been the focus of R&D in recent years.The recombinant adeno-associated virus vector gene therapy of GLP-1 analogues is a new trend of R&D,its current safety,patients'adherence and solutions are proposed in this study.

关 键 词：胰高血糖素样肽-1类似物 葡萄糖依赖性促胰岛素释放多肽受体 胰高血糖素受体 2型糖尿病 

分 类 号：R977.15[医药卫生—药品]