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Development of RelB-targeting small-molecule inhibitors of non-canonical NF-kB signaling with antitumor efficacy

文献类型：期刊论文

作者Li, Cuifeng2,3,4; Wei, Shuqi4; Sun, Donglin1,4; Yang, Zhuo8; Wang, Qi3,4; Lin, Han4; Zhang, Haohao3,4; Hu, Yiming3,4; Liu, Dandan3,4; Ye, Deji3,4
刊名MOLECULAR THERAPY
出版日期2025-04-02
卷号33期号:4页码:1519-1534
ISSN号1525-0016
DOI10.1016/j.ymthe.2025.01.048
通讯作者Jiang, Yuhang(xhaka2016@163.com) ; Zhu, Weiliang(wlzhu@simm.ac.cn) ; Zhang, Xiaoren(xrzhang@gzhmu.edu.cn)
英文摘要Dysfunction of the non-canonical nuclear factor KB (NF-KB) signaling pathway has been causally associated with numbers of cancers and autoimmune diseases. However, specific inhibitors for this signaling pathway remain to be developed. Here, we showed that structure-based cell-based screening yielded a potent and specific small molecule targeting RelB to inhibit the non-canonical NF-KB signaling pathway, while it had no inhibitory effect on the canonical NF-KB signaling pathway. Mechanistically, the inhibitor directly interacted with RelB protein and disrupted RelB binding to its target DNA, thus repressing RelB transactivity on target genes. Through blocking oncogenic activity of the non-canonical NF-KB signaling pathway in colorectal cancer or B lymphoma, the inhibitor efficiently exerted a potent antitumor effect in vitro and in vivo. Thus, our study provided a new RelB-targeting inhibitor that inhibited the non-canonical NF-KB signaling pathway and facilitated precise therapeutic applications in cancers and possibly other diseases.
WOS关键词KAPPA-B PATHWAY ; NF-KAPPA-B2 P52 ; CANCER ; ACTIVATION ; PROMOTER ; DOMAIN ; DEATH
资助项目National Program on Key Research[2018YFA0107500] ; National Program on Key Research[2016YFC1302400] ; National Natural Science Foundation of China[32370894] ; National Natural Science Foundation of China[91949102] ; National Natural Science Foundation of China[91742113] ; National Natural Science Foundation of China[31570902] ; National Natural Science Foundation of China[81771752] ; National Natural Science Foundation of China[31370881] ; Guangzhou Key Medical Discipline Construction Project Fund
WOS研究方向Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
语种英语
WOS记录号WOS:001462883700001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/316974]  
专题中国科学院上海药物研究所
通讯作者Jiang, Yuhang; Zhu, Weiliang; Zhang, Xiaoren
作者单位1.Southern Med Univ, Shenzhen Hosp, Dept Neurol, Shenzhen 518000, Peoples R China
2.Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China
3.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai 200031, Peoples R China
4.Guangzhou Med Univ, Guangdong Hong Kong Macau Joint Lab Cell Fate Regu, Guangdong Prov Key Lab Allergy & Clin Immunol, GMU GIBH Joint Sch Life Sci,Affiliated Hosp 2,Affi, Guangzhou 510000, Peoples R China
5.Sun Yat Sen Univ, Affiliated Hosp 8, Dept Orthoped, Shenzhen 518033, Peoples R China
6.Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, State Key Lab Syst Med Canc,Shanghai Canc Inst, Shanghai 200032, Peoples R China
7.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr TCM Chem Biol, Shanghai 201203, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res,Univ Chinese Acad Sci, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Li, Cuifeng,Wei, Shuqi,Sun, Donglin,et al. Development of RelB-targeting small-molecule inhibitors of non-canonical NF-kB signaling with antitumor efficacy[J]. MOLECULAR THERAPY,2025,33(4):1519-1534.
APA Li, Cuifeng.,Wei, Shuqi.,Sun, Donglin.,Yang, Zhuo.,Wang, Qi.,...&Zhang, Xiaoren.(2025).Development of RelB-targeting small-molecule inhibitors of non-canonical NF-kB signaling with antitumor efficacy.MOLECULAR THERAPY,33(4),1519-1534.
MLA Li, Cuifeng,et al."Development of RelB-targeting small-molecule inhibitors of non-canonical NF-kB signaling with antitumor efficacy".MOLECULAR THERAPY 33.4(2025):1519-1534.

入库方式： OAI收割

来源：上海药物研究所

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