ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Development of RelB-targeting small-molecule inhibitors of non-canonical NF-κB signaling with antitumor efficacy.
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Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Inflammation and carcinogenesis: molecular targets and small-molecule intervention strategies.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Non-canonical NF-κB drives a fate switch from germinal center to early effector B cells.iScience · 2026Article
- Targeting NF-κB signaling for HIV latency reversal: Mechanisms, challenges, and therapeutic perspectives.Virus research · 2026Review
- Microbial metabolic profiling reshapes NF-κB-mediated immune metabolic network: a new mechanism for CRC development.Journal of translational medicine · 2026Review
- Ferrum@albumin assembled nanoclusters inhibit NF-Acta pharmaceutica Sinica. B · 2025Article
- Quantitative Analysis of Monocyte-Derived Macrophage NFκB Signaling in Cancer Co-culture Models Using Luciferase-Based Biosensing.Cellular and molecular bioengineering · 2025Article
- Advances in pharmacological research on myocardial remodeling agents: A decade in review.Medicine · 2025Review
- Dual-edged mechanisms of α-tomatine in hepatocellular carcinoma by suppression of Wnt/β-catenin signaling versus RelB-Driven resistance in tumor therapy.Frontiers in pharmacology · 2025Article
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Authors and funding
24 authors.
Cuifeng LiThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
Shuqi WeiThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China.
Donglin SunThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China; Department of Urology, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, China.
Zhuo YangCAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 201203, China.
Qi WangThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Han LinThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China.
Haohao ZhangThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Yiming HuThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Dandan LiuThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Deji YeThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Yu TaoCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Zhanjie LiuCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Zhijian XuCAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 201203, China.
Bo LiCAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 201203, China.
Lingling LiCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Jie ZhangCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xi ChenThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ningxia XieThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Yufang ShiCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Sanhong LiuCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Yongzhong LiuState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200032, China.
Yuhang JiangThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518033, China. Electronic address: xhaka2016@163.com.
Weiliang ZhuCAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: wlzhu@simm.ac.cn.
Xiaoren ZhangThe Second Affiliated Hospital, The Sixth Affiliated Hospital, Affiliated Cancer Hospital and Institute, GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou 510000, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: xrzhang@gzhmu.edu.cn.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysfunction of the non-canonical nuclear factor κB (NF-κB) 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-κB signaling pathway, while it had no inhibitory effect on the canonical NF-κB 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-κB 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-κB signaling pathway and facilitated precise therapeutic applications in cancers and possibly other diseases.
Indexed as
Antineoplastic AgentsNF-kappa BSignal TransductionSmall Molecule LibrariesTranscription Factor RelBAnimalsCell Line, TumorHumansMiceProtein BindingXenograft Model Antitumor AssaysAntineoplastic AgentsNF-kappa BRELB protein, humanSmall Molecule LibrariesTranscription Factor RelBB lymphomacolorectal cancerinhibitornon-canonical NF-κBRelBRS47tumorigenesis
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