ArticleFree radical biology & medicine2011
Inhibition of thioredoxin reductase 1 by porphyrins and other small molecules identified by a high-throughput screening assay.
Article in Free radical biology & medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 43 citations in OpenAlex.
- Context‑dependent targeting of thioredoxin reductase 1 in cancer: a mechanistic review.Magyar onkologia · 2026Review
- What lies beyond thioredoxin reductase? Cyclometallated gold compounds reveal Sec selectivity in glutathione peroxidases.Free radical biology & medicine · 2026Article
- Porphyrin-coated gold nanoparticles associated with X-rays and proton therapy in the treatment of triple-negative breast cancer.Nanoscale advances · 2026Article
- The "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.Journal of medicinal chemistry · 2024Review
- The Therapeutic Potential of the Restoration of the p53 Protein Family Members in theInternational journal of molecular sciences · 2022Review
- Article
- Effects of pre-partum dietary crude protein level on colostrum fat globule membrane proteins and the performance of Hu ewes and their offspring.Frontiers in veterinary science · 2022Article
- Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death.Antioxidants (Basel, Switzerland) · 2021Article
- Effects of Mammalian Thioredoxin Reductase Inhibitors.Handbook of experimental pharmacology · 2021Article
- Activation of TAp73 and inhibition of TrxR by Verteporfin for improved cancer therapy inFuture science OA · 2019Article
- Protoporphyrin IX is a dual inhibitor of p53/MDM2 and p53/MDM4 interactions and induces apoptosis in B-cell chronic lymphocytic leukemia cells.Cell death discovery · 2019Article
- Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy.Science translational medicine · 2018Article
- Malpighian Tubules as Novel Targets for Mosquito Control.International journal of environmental research and public health · 2017Review
- Redox effects and cytotoxic profiles of MJ25 and auranofin towards malignant melanoma cells.Oncotarget · 2015Article
- Thioredoxin reductase and its inhibitors.Current protein & peptide science · 2014Review
- Identification of Michael acceptor-centric pharmacophores with substituents that yield strong thioredoxin reductase inhibitory character correlated to antiproliferative activity.Antioxidants & redox signaling · 2013Article
- Exposure to silver nanoparticles inhibits selenoprotein synthesis and the activity of thioredoxin reductase.Environmental health perspectives · 2012Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The selenoprotein thioredoxin reductase 1 (TrxR1) has in recent years been identified as a promising anticancer drug target. A high-throughput assay for discovery of novel compounds targeting the enzyme is therefore warranted. Herein, we describe a single-enzyme, dual-purpose assay for simultaneous identification of inhibitors and substrates of TrxR1. Using this assay to screen the LOPAC¹²⁸⁰ compound collection we identified several known inhibitors of TrxR1, thus validating the assay, as well as several compounds hitherto unknown to target the enzyme. These included rottlerin (previously reported as a PKCδ inhibitor and mitochondrial uncoupler) and the heme precursor protoporphyrin IX (PpIX). We found that PpIX was a potent competitive inhibitor of TrxR1, with a K(i)=2.7 μM with regard to Trx1, and in the absence of Trx1 displayed time-dependent irreversible inhibition with an apparent second-order rate constant (k(inact)) of (0.73 ± 0.07) × 10⁻³ μM⁻¹ min⁻¹. Exogenously delivered PpIX was cytotoxic, inhibited A549 cell proliferation, and was found to also inhibit cellular TrxR activity. Hemin and the ferrochelatase inhibitor NMPP also inhibited TrxR1 and showed cytotoxicity, but less potently compared to PpIX. We conclude that rottlerin-induced cellular effects may involve targeting of TrxR1. The unexpected finding of PpIX as a TrxR1 inhibitor suggests that such inhibition may contribute to symptoms associated with conditions of abnormally high PpIX levels, such as reduced ferrochelatase activity seen in erythropoietic protoporphyria. Finally, additional inhibitors of TrxR1 may be discovered and further characterized based upon the new high-throughput TrxR1 assay presented here.
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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.