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Phenotypic screening-based drug discovery of furan-2-carboxylic acid derivatives for the amelioration of type 2 diabetes mellitus (T2DM)

文献类型：期刊论文

作者Chen, Lili1,2; Huang, Suling1; Ye, Yangliang1; Shen, Yu1; Xu, Tifei1; Qin, Li1; Du, Lili1; Leng, Ying1; Shen, Jianhua1
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2023-01-15
卷号246页码:11
ISSN号0223-5234
关键词Phenotypic screening Gluconeogenesis Furan-2-carboxylic acid T2DM
DOI10.1016/j.ejmech.2022.114994
通讯作者Leng, Ying() ; Shen, Jianhua(jhshen@simm.ac.cn)
英文摘要Phenotypic screening still plays an important role in discovering new drugs, especially for diseases with complex pathogenesis, such as diabetes. As excessive gluconeogenesis is considered an important factor in the occurrence of hyperglycemia in T2DM, we previously screened our compounds library for active molecules which inhibit gluconeogenesis, resulting in the discovery of SL010110 with a unique mechanism, different from metformin and a thienopyridine derivative (DMT). The SARs study of SL010110 led to the discovery of 10v. Compared with SL010110, 10v showed improved anti-gluconeogenesis potency and pyruvate tolerance. A further pharmaco-kinetic study demonstrated that 10v displayed a relatively short half-life, moderate volume of distribution, and moderate to high oral bioavailability. In vivo chronic experiments showed an improved capability of 10v in ameliorating hyperglycemia as the 5 mg/kg 10v treatment greatly reduced non-fasting and fasting blood glucose levels, making it a promising candidate for the treatment of T2DM. The progression from in vitro screening to in vivo testing of the derivatized compounds provided a useful phenotypic screening drug discovery strategy based on the inhibition of gluconeogenesis.
WOS关键词GLUCONEOGENESIS ; METFORMIN ; GLUCOSE
资助项目Science andTechnology Commission of Shanghai Municipality (STCSM) ; Shanghai Science and Technology Committee ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica ; [19431900900] ; [21DZ2291100]
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:000901975200001
源URL[http://119.78.100.183/handle/2S10ELR8/304162]  
专题新药研究国家重点实验室
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, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Lili,Huang, Suling,Ye, Yangliang,et al. Phenotypic screening-based drug discovery of furan-2-carboxylic acid derivatives for the amelioration of type 2 diabetes mellitus (T2DM)[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2023,246:11.
APA Chen, Lili.,Huang, Suling.,Ye, Yangliang.,Shen, Yu.,Xu, Tifei.,...&Shen, Jianhua.(2023).Phenotypic screening-based drug discovery of furan-2-carboxylic acid derivatives for the amelioration of type 2 diabetes mellitus (T2DM).EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,246,11.
MLA Chen, Lili,et al."Phenotypic screening-based drug discovery of furan-2-carboxylic acid derivatives for the amelioration of type 2 diabetes mellitus (T2DM)".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 246(2023):11.

入库方式： OAI收割

来源：上海药物研究所

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