ArticleCell chemical biology2019
Frenolicin B Targets Peroxiredoxin 1 and Glutaredoxin 3 to Trigger ROS/4E-BP1-Mediated Antitumor Effects.
Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Thiofrenomycins, new kalafungin-type pyranonaphthoquinone skeleton with sulfide linkage from Streptomyces sp. MM863L-181F9.The Journal of antibiotics · 2026Article
- Mechanism-based peroxiredoxin 3 inhibitors exploit a covalent warhead for cancer therapy.Science advances · 2025Article
- Beyond Antioxidants: How Redox Pathways Shape Cellular Signaling and Disease Outcomes.Antioxidants (Basel, Switzerland) · 2025Review
- A new perspective on iron-dependent cell death: PRDX-1-mediated ferroptosis in tumor cells.Apoptosis : an international journal on programmed cell death · 2025Review
- Discovery of Natural Resorcylic Acid Lactones as Novel Potent Copper Ionophores Covalently Targeting PRDX1 to Induce Cuproptosis for Triple-Negative Breast Cancer Therapy.ACS central science · 2025Article
- Discovery of novel and potent celastrol derivatives as PRDX1 inhibitors for cancer therapy through structure-based virtual screening.Frontiers in pharmacology · 2025Article
- Biochemical and Structural Studies of the Carminomycin 4-Journal of natural products · 2024Article
- Auranofin and reactive oxygen species inhibit protein synthesis and regulate the level of the PLK1 protein in Ewing sarcoma cells.Frontiers in oncology · 2024Article
- Critical Role of the Sulfiredoxin-Peroxiredoxin IV Axis in Urethane-Induced Non-Small Cell Lung Cancer.Antioxidants (Basel, Switzerland) · 2023Article
- Article
- Chemical-proteomics Identify Peroxiredoxin-1 as an Actionable Target in Triple-negative Breast Cancer.International journal of biological sciences · 2023Article
- Essential Roles of Peroxiredoxin IV in Inflammation and Cancer.Molecules (Basel, Switzerland) · 2022Review
- Peroxiredoxin, Senescence, and Cancer.Cells · 2022Review
- Redox-Related Proteins in Melanoma Progression.Antioxidants (Basel, Switzerland) · 2022Article
- GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma.BMC cancer · 2021Article
- Lonicerin targets EZH2 to alleviate ulcerative colitis by autophagy-mediated NLRP3 inflammasome inactivation.Acta pharmaceutica Sinica. B · 2021Article
- Himalaquinones A-G, Angucyclinone-Derived Metabolites Produced by the Himalayan IsolateJournal of natural products · 2021Article
- Glutaredoxin: Discovery, redox defense and much more.Redox biology · 2021Review
- Genetic Inactivation of Peroxiredoxin-I Impairs the Growth of Human Pancreatic Cancer Cells.Antioxidants (Basel, Switzerland) · 2021Article
- Cloning, Expression, Characterization, and Antioxidant Protection of Glutaredoxin3 From Psychrophilic BacteriumFrontiers in microbiology · 2021Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
Abstract
Peroxiredoxin 1 (Prx1) and glutaredoxin 3 (Grx3) are two major antioxidant proteins that play a critical role in maintaining redox homeostasis for tumor progression. Here, we identify the prototypical pyranonaphthoquinone natural product frenolicin B (FB) as a selective inhibitor of Prx1 and Grx3 through covalent modification of active-site cysteines. FB-targeted inhibition of Prx1 and Grx3 results in a decrease in cellular glutathione levels, an increase of reactive oxygen species (ROS), and concomitant inhibition of cancer cell growth, largely by activating the peroxisome-bound tuberous sclerosis complex to inhibit mTORC1/4E-BP1 signaling axis. FB structure-activity relationship studies reveal a positive correlation between inhibition of 4E-BP1 phosphorylation, ROS-mediated cancer cell cytotoxicity, and suppression of tumor growth in vivo. These findings establish FB as the most potent Prx1/Grx3 inhibitor reported to date and also notably highlight 4E-BP1 phosphorylation status as a potential predictive marker in response to ROS-based therapies in cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.