ArticleScience advances2020
Irreversible TrxR1 inhibitors block STAT3 activity and induce cancer cell death.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
31 citing papers in PubMed, 72 citations in OpenAlex.
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- Structure-based identification of a non-covalent thioredoxin reductase inhibitor with proven ADMET suitability.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- The Role of Pomegranate (Food science & nutrition · 2025Review
- Re-Sensitization of Resistant Ovarian Cancer SKOV3/CDDP Cells to Cisplatin by Curcumin Pre-Treatment.International journal of molecular sciences · 2025Article
- Reactive oxygen species: Janus-faced molecules in the era of modern cancer therapy.Journal for immunotherapy of cancer · 2024Review
- Anti-cancer potential of casein and its derivatives: novel strategies for cancer treatment.Medical oncology (Northwood, London, England) · 2024Review
- Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application.Asian journal of pharmaceutical sciences · 2024Article
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- PSMD12 promotes non-small cell lung cancer progression through activating the Nrf2/TrxR1 pathway.Genes & genomics · 2024Article
- Combination of TrxR1 inhibitor and lenvatinib triggers ROS-dependent cell death in human lung cancer cells.International journal of biological sciences · 2024Article
- Fluorescent Probes for Mammalian Thioredoxin Reductase: Mechanistic Analysis, Construction Strategies, and Future Perspectives.Biosensors · 2023Review
- Review
- Potentiation of Cisplatin Cytotoxicity in Resistant Ovarian Cancer SKOV3/Cisplatin Cells by Quercetin Pre-Treatment.International journal of molecular sciences · 2023Article
- GDF15 Promotes Cell Growth, Migration, and Invasion in Gastric Cancer by Inducing STAT3 Activation.International journal of molecular sciences · 2023Article
- Nuclear translocation of thioredoxin-1 promotes colorectal cancer development via modulation of the IL-6/STAT3 signaling axis through interaction with STAT3.Theranostics · 2023Article
- Chemical-proteomics Identify Peroxiredoxin-1 as an Actionable Target in Triple-negative Breast Cancer.International journal of biological sciences · 2023Article
- Immunomodulatory Role of Thioredoxin Interacting Protein in Cancer's Impediments: Current Understanding and Therapeutic Implications.Vaccines · 2022Review
- Cyclic 5-membered disulfides are not selective substrates of thioredoxin reductase, but are opened nonspecifically.Nature communications · 2022Article
- Bone morphogenetic protein 10 alleviates doxorubicin-induced cardiac injury via signal transducer and activator of transcription 3 signaling pathway.Bioengineered · 2022Article
- Role of STAT3 in the pathogenesis of nasopharyngeal carcinoma and its significance in anticancer therapy.Frontiers in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Because of its key role in cancer development and progression, STAT3 has become an attractive target for developing new cancer therapeutics. While several STAT3 inhibitors have progressed to advanced stages of development, their underlying biology and mechanisms of action are often more complex than would be expected from specific binding to STAT3. Here, we have identified and optimized a series of compounds that block STAT3-dependent luciferase expression with nanomolar potency. Unexpectedly, our lead compounds did not bind to cellular STAT3 but to another prominent anticancer drug target, TrxR1. We further identified that TrxR1 inhibition induced Prx2 and STAT3 oxidation, which subsequently blocked STAT3-dependent transcription. Moreover, previously identified inhibitors of STAT3 were also found to inhibit TrxR1, and likewise, established TrxR1 inhibitors block STAT3-dependent transcriptional activity. These results provide new insights into the complexities of STAT3 redox regulation while highlighting a novel mechanism to block aberrant STAT3 signaling in cancer cells.
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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.