Targeting STING oligomerization with licochalcone D ameliorates STING-driven inflammatory diseases
文献类型：期刊论文
| 作者 | Zhang, Yinghui7,8; Liu, Yadan6,8; Jiang, Bing6; Chen, Lifan7,8; Hu, Jie6; Niu, Buying7,8; Chang, Jie8; Fan, Zisheng3,4,8; Zhou, Jingyi2,8; Wang, Yajie5,7 |
| 刊名 | SCIENCE CHINA-LIFE SCIENCES
 |
| 出版日期 | 2024-08-22 |
| 页码 | 14 |
| 关键词 | cGAS-STING signaling STING inhibitor TransformerCPI model Licochalcone D inflammatory diseases |
| ISSN号 | 1674-7305 |
| DOI | 10.1007/s11427-024-2703-6 |
| 通讯作者 | Yang, Ruirui(yangruirui@simm.ac.cn) ; Zheng, Mingyue(myzheng@simm.ac.cn) ; Zhang, Sulin(slzhang@simm.ac.cn) |
| 英文摘要 | The development of STING inhibitors for the treatment of STING-related inflammatory diseases continues to encounter significant challenges. The activation of STING is a multi-step process that includes binding with cGAMP, self-oligomerization, and translocation from the endoplasmic reticulum to the Golgi apparatus, ultimately inducing the expression of IRF3 and NF-kappa B-mediated interferons and inflammatory cytokines. It has been demonstrated that disruption of any of these steps can effectively inhibit STING activation. Traditional structure-based drug screening methodologies generally focus on specific binding sites. In this study, a TransformerCPI model based on protein primary sequences and independent of binding sites is employed to identify compounds capable of binding to the STING protein. The natural product Licochalcone D (LicoD) is identified as a potent and selective STING inhibitor. LicoD does not bind to the classical ligand-binding pocket; instead, it covalently modifies the Cys148 residue of STING. This modification inhibits STING oligomerization, consequently suppressing the recruitment of TBK1 and the nuclear translocation of IRF3 and NF-kappa B. LicoD treatment ameliorates the inflammatory phenotype in Trex1-1- mice and inhibits the progression of DSS-induced colitis and AOM/DSS-induced colitis-associated colon cancer (CAC). In summary, this study reveals the potential of LicoD in treating STING-driven inflammatory diseases. It also demonstrates the utility of the TransformerCPI model in discovering allosteric compounds beyond the conventional binding pockets. |
| WOS关键词 | CYCLIC GMP-AMP ; NF-KAPPA-B ; CGAS ; 2ND-MESSENGER ; ACTIVATION ; INDUCTION ; INFECTION |
| 资助项目 | National Natural Science Foundation of China[T2225002] ; National Natural Science Foundation of China[82273855] ; National Natural Science Foundation of China[82304379] ; National Natural Science Foundation of China[81903639] ; National Key Research and Development Program of China[2022YFC3400504] ; Youth Innovation Promotion Association CAS[2023296] ; SIMM-SHUTCM Traditional Chinese Medicine Innovation Joint Research Program[E2G805H] ; Open fund of state key laboratory of Pharmaceutical Biotechnology, Nanjing University, China[KF-202301] ; Natural Science Foundation of Shanghai[22ZR1474300] ; Lingang Laboratory[LG202102-01-02] ; Lingang Laboratory[LG-QS-202204-01] ; Young Elite Scientists Sponsorship Program by CAST[2023QNRC001] |
| WOS研究方向 | Life Sciences & Biomedicine - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001299747400003 |
| 出版者 | SCIENCE PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/313026]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Yang, Ruirui; Zheng, Mingyue; Zhang, Sulin |
| 作者单位 | 1.Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Peoples R China 2.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 200031, Peoples R China 3.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 4.Shanghai Tech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 200031, Peoples R China 5.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 8.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Yinghui,Liu, Yadan,Jiang, Bing,et al. Targeting STING oligomerization with licochalcone D ameliorates STING-driven inflammatory diseases[J]. SCIENCE CHINA-LIFE SCIENCES,2024:14. |
| APA | Zhang, Yinghui.,Liu, Yadan.,Jiang, Bing.,Chen, Lifan.,Hu, Jie.,...&Zhang, Sulin.(2024).Targeting STING oligomerization with licochalcone D ameliorates STING-driven inflammatory diseases.SCIENCE CHINA-LIFE SCIENCES,14. |
| MLA | Zhang, Yinghui,et al."Targeting STING oligomerization with licochalcone D ameliorates STING-driven inflammatory diseases".SCIENCE CHINA-LIFE SCIENCES (2024):14. |
入库方式： OAI收割
来源：上海药物研究所
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