Evidence map›Paper›PMID 29444979›Full record

ArticleScience translational medicine2018

Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy.

William C Stafford, Xiaoxiao Peng, Maria Hägg Olofsson, Xiaonan Zhang, Diane K Luci, Li Lu, Qing Cheng, Lionel Trésaugues, Thomas S Dexheimer, Nathan P Coussens and 10 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
10.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 236 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Multifunctional auranofin analogues: dual-targeting TSPO/TrxR gold(I) complexes with activity in resistant ovarian cancer.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 4 countries.

William C StaffordDivision of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77 Stockholm, Sweden.ORCID 0000-0003-4937-4161
Xiaoxiao PengDivision of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77 Stockholm, Sweden.
Maria Hägg OlofssonDepartment of Oncology-Pathology, Karolinska Institutet, SE 171 77 Stockholm, Sweden.
Xiaonan ZhangDepartment of Oncology-Pathology, Karolinska Institutet, SE 171 77 Stockholm, Sweden.
Diane K LuciNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-4874, USA.ORCID 0000-0001-5728-0398
Li LuKarolinska Experimental Research and Imaging Center, Karolinska University Hospital, SE 171 76 Stockholm, Sweden.
Qing ChengDivision of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77 Stockholm, Sweden.ORCID 0000-0002-3170-9333
Lionel TrésauguesDivision of Biophysics, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77 Stockholm, Sweden.ORCID 0000-0002-1395-8416
Thomas S DexheimerNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-4874, USA.ORCID 0000-0002-6444-3121
Nathan P CoussensNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-4874, USA.ORCID 0000-0002-3896-7909
Martin AugstenDepartment of Oncology-Pathology, Karolinska Institutet, SE 171 77 Stockholm, Sweden.ORCID 0000-0001-5963-8197
Hanna-Stina Martinsson AhlzénDivision of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77 Stockholm, Sweden.
Owe OrwarOblique Therapeutics AB, SE 413 46 Gothenburg, Sweden.
Arne ÖstmanDepartment of Oncology-Pathology, Karolinska Institutet, SE 171 77 Stockholm, Sweden.ORCID 0000-0003-3993-0021
Sharon Stone-ElanderDepartment of Neuroradiology, Positron Emission Tomography Radiochemistry, Karolinska University Hospital, SE 171 76 Stockholm, Sweden.
David J MaloneyNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-4874, USA.
Ajit JadhavNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-4874, USA.ORCID 0000-0001-7955-1451
Anton SimeonovNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-4874, USA.
Stig LinderDepartment of Oncology-Pathology, Karolinska Institutet, SE 171 77 Stockholm, Sweden.ORCID 0000-0002-4952-445X
Elias S J ArnérDivision of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77 Stockholm, Sweden. elias.arner@ki.se.ORCID 0000-0002-4807-6114
Karolinska Institutet · SENational Center for Advancing Translational Sciences · USKarolinska University Hospital · SELinköping University · SEScience for Life Laboratory · SE

Funding

Small molecule screening programZ01HG200319 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI AUSTIN, CHRISTOPHER P · 2004 to 2008
$32.3M
HTS FOR DRUG LEADS TARGETING THE MAMMALIAN SELENOPROTEIN THIOREDOXIN REDUCTASE 1R03MH090846 · NIMH · KAROLINSKA INSTITUTE · PI ARNER, ELIAS S.J. · 2010 to 2011
$50k
Intramural NIH HHS Z01 HG200319NIMH NIH HHS R03 MH090846
6 · The paper itself

Abstract

Cancer cells adapt to their inherently increased oxidative stress through activation of the glutathione (GSH) and thioredoxin (TXN) systems. Inhibition of both of these systems effectively kills cancer cells, but such broad inhibition of antioxidant activity also kills normal cells, which is highly unwanted in a clinical setting. We therefore evaluated targeting of the TXN pathway alone and, more specifically, selective inhibition of the cytosolic selenocysteine-containing enzyme TXN reductase 1 (TXNRD1). TXNRD1 inhibitors were discovered in a large screening effort and displayed increased specificity compared to pan-TXNRD inhibitors, such as auranofin, that also inhibit the mitochondrial enzyme TXNRD2 and additional targets. For our lead compounds, TXNRD1 inhibition correlated with cancer cell cytotoxicity, and inhibitor-triggered conversion of TXNRD1 from an antioxidant to a pro-oxidant enzyme correlated with corresponding increases in cellular production of H

Indexed as

AnimalsAntioxidantsCell DeathCell Line, TumorCytosolEnzyme InhibitorsHigh-Throughput Screening AssaysHydrogen PeroxideMaleMice, SCIDNeoplasmsOxidation-ReductionStructure-Activity RelationshipThioredoxin Reductase 1Xenograft Model Antitumor AssaysAntioxidantsEnzyme InhibitorsHydrogen PeroxideThioredoxin Reductase 1

Identifiers

PMID29444979
PMCPMC7059553
OpenAlexW2785337616

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.