G蛋白偶联胆汁酸受体1激动剂研究进展  

Advances in the study of TGR5 agonists

作　　者：李占山 宫思邈 廖琦 韩竹箴[1] 王峥涛[1] LI Zhanshan;GONG Simiao;LIAO Qi;HAN Zhuzhen;WANG Zhengtao(Institute of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学中药研究所,上海201203 [2]上海中医药大学附属岳阳中西医结合医院,上海200437

出　　处：《陕西医学杂志》2025年第3期413-423,共11页Shaanxi Medical Journal

基　　金：国家自然科学基金资助国际(地区)合作与交流项目(81920108033)。

摘　　要：G蛋白偶联胆汁酸受体1(TGR5)激活通过多个信号转导通路影响糖脂代谢、能量代谢、炎症反应和内源性信号分子表达,在代谢性疾病和炎症性疾病的治疗中有着巨大的潜力。多个针对TGR5的药物已进入临床研究阶段,但由于不良反应明显,大规模临床应用受到限制。现将TGR5激动剂按内源性胆汁酸类、合成小分子药物和天然产物激动剂三类进行阐述,并针对TGR5靶点对天然产物结构优势进行分析,意在挑选合适的天然活性物质做作为先导化合物,为开发高效低毒的TGR5激动剂提供思路与参考。The G protein-coupled bile acid receptor 1(TGR5)activation affects glycolipid metabolism,energy metabolism,inflammatory response and endogenous signaling molecule expression through multiple signaling pathways,which has great potential in the treatment of metabolic and inflammatory diseases.Multiple drugs targeting TGR5 have entered the clinical research stage,but their large-scale clinical use has been limited due to their obvious side effects.TGR5 agonists are classified into three categories:endogenous bile acids,synthetic small molecules and natural product agonists.We also analyzed the structural advantages of natural products for TGR5 targets,with the intention of selecting suitable natural active substances as lead compounds and providing ideas and references for the development of highly efficient and low-toxic TGR5 agonists.

关 键 词：G蛋白偶联胆汁酸受体1 内源性胆汁酸及其类似物 合成小分子药物 结构修饰 天然产物 先导化合物 

分 类 号：R914[医药卫生—药物化学]