Design of G-protein-coupled bile acid receptor 1 (GPBAR1, TGR5) soft drugs with reduced gallbladder-filling effects

doi:10.1016/j.ejmech.2020.112619

	Design of G-protein-coupled bile acid receptor 1 (GPBAR1, TGR5) soft drugs with reduced gallbladder-filling effects
	Han, Fanghui 1,2; Ning, Mengmeng 1; Cao, Hua 1; Ye, Yangliang 1; Feng, Ying 1; Leng, Ying 1,2; Shen, Jianhua 1,2
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2020-10-01
卷号	203 页码:12
关键词	Soft drug TGR5 GLP-1 Gallbladder-filling effects Rapid metabolism Carboxylic ester
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2020.112619
通讯作者	Leng, Ying(yleng@simm.ac.cn) ; Shen, Jianhua(jhshen@simm.ac.cn)
英文摘要	The G-protein-coupled bile acid receptor TGR5 agonists were widely developed in type 2 diabetes and gastrointestinal disorders, but were also full of challenges, due to the systemic on-targeted side effects, especially the gallbladder-filling effects. Here, to circumvent these risks, several TGR5 agonists with soft-drug designation had been designed and synthesized with the properties of rapid metabolized after drug effect. Among them, compound 19 showed negligible systemic exposure and favorable gallbladder safety on a 3-day continuous administration, providing a novel strategy for developing TGR5 agonists. (C) 2020 Elsevier Masson SAS. All rights reserved.
资助项目	Science and Technology Commission of Shanghai Municipality (STCSM)[19431900900] ; Chinese Academy of Sciences[XDA12040309] ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica
WOS关键词	GLUCAGON-LIKE PEPTIDE-1 ; PHYSIOLOGY ; SECRETION ; DISCOVERY ; AGONISTS ; POTENT ; PHARMACOLOGY ; DERIVATIVES ; MECHANISMS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000568867400034
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291130]
专题	中国科学院上海药物研究所
通讯作者	Leng, Ying; Shen, Jianhua
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Han, Fanghui,Ning, Mengmeng,Cao, Hua,et al. Design of G-protein-coupled bile acid receptor 1 (GPBAR1, TGR5) soft drugs with reduced gallbladder-filling effects[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2020,203:12.
APA	Han, Fanghui.,Ning, Mengmeng.,Cao, Hua.,Ye, Yangliang.,Feng, Ying.,...&Shen, Jianhua.(2020).Design of G-protein-coupled bile acid receptor 1 (GPBAR1, TGR5) soft drugs with reduced gallbladder-filling effects.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,203,12.
MLA	Han, Fanghui,et al."Design of G-protein-coupled bile acid receptor 1 (GPBAR1, TGR5) soft drugs with reduced gallbladder-filling effects".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 203(2020):12.