Discovery of indole derivatives as STING degraders
文献类型：期刊论文
| 作者 | An, Yuxiang3,5; Zhang, Yan4; Luo, Xin2; Lan, Yaohan3,5; Geng, Meiyu1,2,4 ; Duan, Wenhu3,5; Xie, Zuoquan3,4; Zhang, Hefeng1,5
|
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2025-09-15 |
| 卷号 | 294页码:21 |
| 关键词 | Autoimmune diseases Degrader Inflammatory PROTAC STING |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2025.117747 |
| 英文摘要 | Aberrant activation of the stimulator of interferon genes (STING) pathway is associated with the development of various inflammatory and autoimmune diseases. Targeting STING for degradation represents a novel strategy for the treatment of these diseases. In this study, we designed and synthesized a series of STING-PROTACs based on a nitro-free covalent warhead and different E3 ligase binders. The representative compound 2h specifically degraded STING protein through the proteasome pathway with a DC50 value of 3.23 mu M and exhibited sustained degradation activity over 72 h. Further biological studies demonstrated that compound 2h inhibited STING signaling and effectively suppressed immune-inflammatory cytokines both in vitro and in vivo. Moreover, compound 2h offered better safety compared to its warhead molecule and SP23. Collectively, compound 2h is a potent nitro-free covalent STING degrader and warrants further investigation. |
| WOS关键词 | CYCLIC DINUCLEOTIDE ; DNA SENSOR ; INNATE ; PROTEINS ; PROTACS |
| 资助项目 | Shanghai Sailing Program[24YF2755500] ; Project of Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM0320231002] ; Shandong Laboratory Program[SYS202205] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001498097600001 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318207]  |
| 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, Jiangsu, Peoples R China 3.Univ Chinese Acad Sci, Sch Pharm, 19A Yuquan Rd, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, 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 | An, Yuxiang,Zhang, Yan,Luo, Xin,et al. Discovery of indole derivatives as STING degraders[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2025,294:21. |
| APA | An, Yuxiang.,Zhang, Yan.,Luo, Xin.,Lan, Yaohan.,Geng, Meiyu.,...&Zhang, Hefeng.(2025).Discovery of indole derivatives as STING degraders.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,294,21. |
| MLA | An, Yuxiang,et al."Discovery of indole derivatives as STING degraders".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 294(2025):21. |
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。