ArticleRedox biology2021
Comprehensive chemical proteomics analyses reveal that the new TRi-1 and TRi-2 compounds are more specific thioredoxin reductase 1 inhibitors than auranofin.
Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Thioredoxin reductase-1 facilitates cellular plasticity and stemness mediated by TGF-β1 in non-small cell lung cancer.Cancer biology & therapy · 2026Article
- PANX2 Suppresses Lung Adenocarcinoma Progression by Inducing Disulfidptosis and Enhancing Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Context‑dependent targeting of thioredoxin reductase 1 in cancer: a mechanistic review.Magyar onkologia · 2026Review
- Redox regulation of EGFR activation by thioredoxin reductase 3 drives resistance to EGFR inhibitors in triple-negative breast cancer.Cell death discovery · 2026Article
- What lies beyond thioredoxin reductase? Cyclometallated gold compounds reveal Sec selectivity in glutathione peroxidases.Free radical biology & medicine · 2026Article
- Tumor-intrinsic metabolic pathways essential for tumorigenesis and resistance to anti-PD1 in oncogenic Kras-driven lung adenocarcinoma.Cancer & metabolism · 2026Article
- Transcriptomic Analysis Reveals an NRF2-Mediated Redox and Metabolic Reprogramming in Sorafenib-Resistant Hepatocellular Carcinoma Cells.Biotech (Basel (Switzerland)) · 2026Article
- Evaluating the Antiproliferative Effects of Tri(2-Furyl)- and Triphenylphosphine-Gold(I) Pyridyl- and Pyrimidine-Thiolate Complexes.Biomolecules · 2026Article
- Structure of the TXNL1-bound proteasome.Nature structural & molecular biology · 2025Article
- The novel thioredoxin reductase inhibitor butaselen suppresses lung cancer by inducing oxidative stress.Redox report : communications in free radical research · 2025Article
- Anti-Tumoral Treatment with Thioredoxin Reductase 1 Inhibitor Auranofin Fosters Regulatory T Cell and B16F10 Expansion in Mice.Antioxidants (Basel, Switzerland) · 2025Article
- Synthesis and in vitro characterization of [EJNMMI radiopharmacy and chemistry · 2025Article
- PK11007 Covalently Inhibits Thioredoxin Reductase 1 to Induce Oxidative Stress and Autophagy Impairment in NSCLC Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and Therapeutic Implications.MedComm · 2025Review
- Thioredoxin Reductase 1 inhibition triggers ferroptosis in KRAS-independent lung cancers.bioRxiv : the preprint server for biology · 2025Article
- Pharmacological Inhibition of TXNRD1 by a Small Molecule Flavonoid Butein Overcomes Cisplatin Resistance in Lung Cancer Cells.Biological trace element research · 2025Article
- HCMV infection downregulates GPX4 and stimulates lipid peroxidation but does not induce ferroptosis.Journal of virology · 2025Article
- Ferroptosis and Its Potential Role in the Physiopathology of Skeletal Muscle Atrophy.International journal of molecular sciences · 2024Review
- The "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.Journal of medicinal chemistry · 2024Review
- Article
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anticancer drugs that target cellular antioxidant systems have recently attracted much attention. Auranofin (AF) is currently evaluated in several clinical trials as an anticancer agent that targets the cytosolic and mitochondrial forms of the selenoprotein thioredoxin reductase, TXNRD1 and TXNRD2. Recently, two novel TXNRD1 inhibitors (TRi-1 and TRi-2) have been developed that showed anticancer efficacy comparable to AF, but with lower mitochondrial toxicity. However, the cellular action mechanisms of these drugs have not yet been thoroughly studied. Here we used several proteomics approaches to determine the effects of AF, TRi-1 and TRi-2 when used at IC50 concentrations with the mouse B16 melanoma and LLC lung adenocarcinoma cells, as these are often used for preclinical mouse models in evaluation of anticancer drugs. The results demonstrate that TRi-1 and TRi-2 are more specific TXNRD1 inhibitors than AF and reveal additional AF-specific effects on the cellular proteome. Interestingly, AF triggered stronger Nrf2-driven antioxidant responses than the other two compounds. Furthermore, AF affected several additional proteins, including GSK3A, GSK3B, MCMBP and EEFSEC, implicating additional effects on glycogen metabolism, cellular differentiation, inflammatory pathways, DNA replication and selenoprotein synthesis processes. Our proteomics data provide a resource for researchers interested in the multidimensional analysis of proteome changes associated with oxidative stress in general, and the effects of TXNRD1 inhibitors and AF protein targets in particular.
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