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. 新药研究国家重点实验室
Design, synthesis, and evaluation of thiazolecarboxamide derivatives as stimulator of interferon gene inhibitors

文献类型：期刊论文

作者Jin, Zechen4,5; Zhang, Yan3; Luo, Xin2,3; Geng, Meiyu1,3; Duan, Wenhu1,4,5; Xie, Zuoquan3; Zhang, Hefeng5
刊名MOLECULAR DIVERSITY
出版日期2024-04-29
页码27
关键词Inflammation Inhibitor Interferon-stimulated gene 15 Stimulator of interferon gene Thiazolecarboxamide
ISSN号1381-1991
DOI10.1007/s11030-024-10860-6
通讯作者Xie, Zuoquan(zqxie@simm.ac.cn) ; Zhang, Hefeng(zhanghefeng1@simm.ac.cn)
英文摘要Stimulator of interferon gene (STING) plays critical roles in the cytoplasmic DNA-sensing pathway and in the induction of inflammatory response. Aberrant cytoplasmic DNA accumulation and STING activation are implicated in numerous inflammatory and autoimmune diseases. Here, we reported the discovery of a series of thiazolecarboxamide-based STING inhibitors through a molecular planarity/symmetry disruption strategy. The privileged compound 15b significantly inhibited STING signaling and suppressed immune-inflammatory cytokine levels in both human and murine cells. In vivo experiments demonstrated 15b effectively ameliorated immune-inflammatory cytokines upregulation in MSA-2-stimulated and Trex1-D18N mice. Furthermore, compound 15b exhibited enhanced efficacy in suppressing interferon-stimulated gene 15 (ISG15), a critical positive feedback regulator of STING. Overall, compound 15b deserves further development for the treatment of STING-associated inflammatory and autoimmune diseases.
WOS关键词INNATE ; SENSOR ; MUTATIONS ; ADAPTER
资助项目China Postdoctoral Science Foundation[2023T160663] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[SIMM0320231002] ; Natural Science Foundation of China for Innovation Research Group[81821005] ; Shanghai Municipal Science and Technology Major Project ; Collaborative Innovation Cluster Project of Shanghai Municipal Commission of Health and Family Planning[2020CXJQ02] ; Shandong Laboratory Program[SYS202205]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001215022300002
出版者SPRINGER
源URL[http://119.78.100.183/handle/2S10ELR8/310879]  
专题新药研究国家重点实验室
通讯作者Xie, Zuoquan; Zhang, Hefeng
作者单位1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xian Lin Rd, Nanjing 210023, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Sch Pharm, 19A Yuquan Rd, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, Small Mol Drug Res Ctr, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Jin, Zechen,Zhang, Yan,Luo, Xin,et al. Design, synthesis, and evaluation of thiazolecarboxamide derivatives as stimulator of interferon gene inhibitors[J]. MOLECULAR DIVERSITY,2024:27.
APA Jin, Zechen.,Zhang, Yan.,Luo, Xin.,Geng, Meiyu.,Duan, Wenhu.,...&Zhang, Hefeng.(2024).Design, synthesis, and evaluation of thiazolecarboxamide derivatives as stimulator of interferon gene inhibitors.MOLECULAR DIVERSITY,27.
MLA Jin, Zechen,et al."Design, synthesis, and evaluation of thiazolecarboxamide derivatives as stimulator of interferon gene inhibitors".MOLECULAR DIVERSITY (2024):27.

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。