Structure-Activity Relationship Study of 1H-Pyrrole-3-carbonitrile Derivatives as STING Receptor Agonists
文献类型：期刊论文
| 作者 | Shen, Chang1,2,3; Xu, Peijia2,4; Zhang, Changfa2,4; Su, Zhaoming2,4; Shan, Bin2; Li, Rui2; Sui, Qibang2,3; Zhang, Keke2,4; Chen, Zhengyang2,3; Zhou, Jingyi2 |
| 刊名 | ACS MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2023-07-12 |
| 页码 | 9 |
| ISSN号 | 1948-5875 |
| 关键词 | cGAS-STING signaling pathway STING agonists antitumor immunity anti-infection immunity |
| DOI | 10.1021/acsmedchemlett.3c00208 |
| 通讯作者 | Zhang, Sulin(slzhang@simm.ac.cn) ; Hou, Hui(houhui@simm.ac.cn) |
| 英文摘要 | The use of small agonists to target stimulators of interferongenes(STING) has been demonstrated to be a promising strategy for the treatmentof various cancers and infectious diseases. Herein, we discovereda series of 1H-pyrrole-3-carbonitrile derivativesas potential STING agonists. On this basis, the structure-activityrelationship of this scaffold was studied by introducing various substituentson the aniline ring system. Representative compounds 7F, 7P, and 7R all displayed comparable activitiesto the reported STING agonist SR-717 in binding various hSTING allelesand induced reporter signal in human THP1 cell lines. Model compound 7F induced phosphorylation of TBK1, IRF3, p65, and STAT3 ina STING-dependent fashion and stimulated the expression of targetgenes IFNB1, CXCL10, and IL6 in a time-dependent manner in human THP1 cells. Ourfindings afforded a series of novel STING agonists with promisingpotential. |
| WOS关键词 | PATHWAY ; ACTIVATION ; CANCER |
| 资助项目 | National Natural Science Foundation of China[T2225002] ; National Natural Science Foundation of China[82273855] ; National Natural Science Foundation of China[91953203] ; Lingang Laboratory[LG202102-01-02] ; Lingang Laboratory[LG-QS-202204-01] ; National Key Research and Development Program of China[2022YFC3400504] ; Youth Innovation Promotion Association CAS[2023296] ; Natural Science Foundation of Shanghai[22ZR1474300] ; SIMM-SHUTCM Traditional Chinese Medicine Innovation Joint Research Program[E2G805H] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:001026993000001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306442]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Sulin; Hou, Hui |
| 作者单位 | 1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shen, Chang,Xu, Peijia,Zhang, Changfa,et al. Structure-Activity Relationship Study of 1H-Pyrrole-3-carbonitrile Derivatives as STING Receptor Agonists[J]. ACS MEDICINAL CHEMISTRY LETTERS,2023:9. |
| APA | Shen, Chang.,Xu, Peijia.,Zhang, Changfa.,Su, Zhaoming.,Shan, Bin.,...&Hou, Hui.(2023).Structure-Activity Relationship Study of 1H-Pyrrole-3-carbonitrile Derivatives as STING Receptor Agonists.ACS MEDICINAL CHEMISTRY LETTERS,9. |
| MLA | Shen, Chang,et al."Structure-Activity Relationship Study of 1H-Pyrrole-3-carbonitrile Derivatives as STING Receptor Agonists".ACS MEDICINAL CHEMISTRY LETTERS (2023):9. |
入库方式： OAI收割
来源：上海药物研究所
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