中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 国家级研究中心
  5. 原创新药研究全国重点实验室
Novel thieno[2,3-b]pyridine derivatives protect islet through DRAK2 kinase inhibition

文献类型：期刊论文

作者Lian, Kaiyue1,5; Li, Ruihan2; Lu, Yuting5; Song, Gaolei5; Zhang, Xinwen5; Zhang, Yuxin1,5; Xu, Honghong5; Sun, Xinyu5; Gu, Min5; Yang, Yang1,3,5
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2026-01-05
卷号301页码:18
关键词DRAK2 Inhibitor Thieno[2 b ]pyridine Diabetes
ISSN号0223-5234
DOI10.1016/j.ejmech.2025.118258
英文摘要DRAK2 (STK17B), a serine/threonine kinase, plays a critical role in apoptosis and has been implicated in metabolic diseases, including type 2 diabetes (T2D) and metabolic dysfunction-associated steatohepatitis (MASH). Previous studies have demonstrated DRAK2's roles in pancreatic (3 cell dysfunction and mitochondrial impairment. This study is dedicated to the development of novel DRAK2 inhibitors aimed at preserving (3 cell function. Through comprehensive structure-activity relationship (SAR) analyses, we synthesized and evaluated a series of compounds, identifying potent inhibitors (represented by Y17) with nanomolar potency. In vitro experiments revealed that these compounds enhanced mitochondrial membrane potential (MMP) in INS-1E cells and glucose-stimulated insulin secretion (GSIS) in primary mouse islets, as well as protecting against palmitic acid (PA)-induced apoptosis. In vivo studies demonstrated the distribution of the compounds in pancreatic tissue and their ability to improve glucose tolerance in mice. Molecular docking analyses elucidated key interactions between the inhibitors and DRAK2. The inhibitors exerted their function particularly via the DRAK2-ULK1 axis, thereby confirming their mechanism of action. Collectively, our findings underscore DRAK2 as a promising therapeutic target for T2D and provide a potential for developing antidiabetic therapies through preserving (3 cell function.
WOS关键词CELL APOPTOSIS ; RESISTANCE ; DISCOVERY ; FAMILY
资助项目National Natural Science Foundation of China[82425058] ; National Natural Science Foundation of China[82200885] ; National Natural Science Foundation of China[82470835] ; Shanghai Rising-Star Program[24QA2701700]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001600931600002
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/319682]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Li, Jingya; Nan, Fajun
作者单位1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
2.Nanjing Univ Chinese Med, Clin Med Coll 1, Nanjing 210023, Peoples R China
3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
4.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Lian, Kaiyue,Li, Ruihan,Lu, Yuting,et al. Novel thieno[2,3-b]pyridine derivatives protect islet through DRAK2 kinase inhibition[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2026,301:18.
APA Lian, Kaiyue.,Li, Ruihan.,Lu, Yuting.,Song, Gaolei.,Zhang, Xinwen.,...&Nan, Fajun.(2026).Novel thieno[2,3-b]pyridine derivatives protect islet through DRAK2 kinase inhibition.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,301,18.
MLA Lian, Kaiyue,et al."Novel thieno[2,3-b]pyridine derivatives protect islet through DRAK2 kinase inhibition".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 301(2026):18.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。