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Photochemically controlled activation of STING by CAIX-targeting photocaged agonists to suppress tumor cell growth

文献类型：期刊论文

作者Ding, Chunyong2,7; Du, Mengyan1,3,6; Xiong, Zhi2,5; Wang, Xue2; Li, Hongji2; He, Ende2; Li, Han3,6; Dang, Yijing4; Lu, Qing2; Li, Shicong2
刊名CHEMICAL SCIENCE
出版日期2023-06-07
卷号14期号:22页码:5956-5964
ISSN号2041-6520
DOI10.1039/d3sc01896b
通讯作者Ding, Chunyong(chunding@sjtu.edu.cn) ; Jing, Lili(lilijing@sjtu.edu.cn) ; Xie, Zuoquan(zqxie@simm.ac.cn) ; Zhang, Ao(ao6919zhang@sjtu.edu.cn)
英文摘要Controllable activation of the innate immune adapter protein - stimulator of interferon genes (STING) pathway is a critical challenge for the clinical development of STING agonists due to the potential "on-target off-tumor" toxicity caused by systematic activation of STING. Herein, we designed and synthesized a photo-caged STING agonist 2 with a tumor cell-targeting carbonic anhydrase inhibitor warhead, which could be readily uncaged by blue light to release the active STING agonist leading to remarkable activation of STING signaling. Furthermore, compound 2 was found to preferentially target tumor cells, stimulate the STING signaling in zebrafish embryo upon photo-uncaging and to induce proliferation of macrophages and upregulation of the mRNA expression of STING as well as its downstream NF-?B and cytokines, thus leading to significant suppression of tumor cell growth in a photo-dependent manner with reduced systemic toxicity. This photo-caged agonist not only provides a powerful tool to precisely trigger STING signalling, but also represents a novel controllable STING activation strategy for safer cancer immunotherapy.
资助项目National Natural Science Foundation of China[21877120] ; National Natural Science Foundation of China[22177068] ; Science and Technology Commission of Shanghai Municipality[21ZR1429100] ; Shanghai Jiao Tong University[AF1700037] ; Shanghai Jiao Tong University[WF220217002] ; Collaborative Innovation Cluster Project of Shanghai Municipal Commission of Health and Family Planning[2020CXJQ02] ; National Key R&D Program of China[81821005] ; National Natural Science Foundation of China for Innovation Research Group ; [2022YFF1203005]
WOS研究方向Chemistry
语种英语
出版者ROYAL SOC CHEMISTRY
WOS记录号WOS:000988813300001
源URL[http://119.78.100.183/handle/2S10ELR8/306617]  
专题新药研究国家重点实验室
通讯作者Ding, Chunyong; Jing, Lili; Xie, Zuoquan; Zhang, Ao
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Shanghai Jiao Tong Univ, Coll Pharmaceut Sci, Shanghai Frontiers Sci Ctr Drug Target Identificat, Natl Key Lab Innovat Immunotherapy, Shanghai 200240, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China
5.Nanchang Univ, Sch Pharm, Jiangxi 330000, Peoples R China
6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
7.Shanghai Jiao Tong Univ, Zhangjiang Inst Adv Study, Shanghai 200240, Peoples R China
推荐引用方式
GB/T 7714		 Ding, Chunyong,Du, Mengyan,Xiong, Zhi,et al. Photochemically controlled activation of STING by CAIX-targeting photocaged agonists to suppress tumor cell growth[J]. CHEMICAL SCIENCE,2023,14(22):5956-5964.
APA Ding, Chunyong.,Du, Mengyan.,Xiong, Zhi.,Wang, Xue.,Li, Hongji.,...&Zhang, Ao.(2023).Photochemically controlled activation of STING by CAIX-targeting photocaged agonists to suppress tumor cell growth.CHEMICAL SCIENCE,14(22),5956-5964.
MLA Ding, Chunyong,et al."Photochemically controlled activation of STING by CAIX-targeting photocaged agonists to suppress tumor cell growth".CHEMICAL SCIENCE 14.22(2023):5956-5964.

入库方式： OAI收割

来源：上海药物研究所

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