ArticleNature communications2022
Cyclic 5-membered disulfides are not selective substrates of thioredoxin reductase, but are opened nonspecifically.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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.
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.
Who cites it
15 citing papers in PubMed, 41 citations in OpenAlex.
- Cyclic Thiosulfinates: Synthesis and Applications in Chemical Biology and Materials Science.Chembiochem : a European journal of chemical biology · 2026Review
- Lipoic Acid Derivative/PEI Composite Nanoparticles Enable Efficient mRNA Delivery via Thiol-Mediated Cellular Uptake.Macromolecular bioscience · 2026Article
- Rational Design, Synthesis, and Systematic Evaluation of Redox-Responsive SN-38 Prodrugs for Selective Activation in Hypoxic Tumor Microenvironments.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Insights into the activation patterns of 1,2-dithiolane unit in biofunctional molecules.Nature communications · 2026Article
- Bicyclic Selenenyl Sulfides with Tuned Bioreductive Step Rates Reveal Constraints for Probes Targeting Thioredoxin Reductase.Angewandte Chemie (International ed. in English) · 2025Article
- Activation of Dithiolopyrrolone Antibiotics by Cellular Reductants.Biochemistry · 2025Article
- The "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.Journal of medicinal chemistry · 2024Review
- Crystal structure of histone deacetylase 6 complexed with (R)-lipoic acid, an essential cofactor in central carbon metabolism.The Journal of biological chemistry · 2023Article
- May 1,2-Dithiolane-4-carboxylic Acid and Its Derivatives Serve as a Specific Thioredoxin Reductase 1 Inhibitor?Molecules (Basel, Switzerland) · 2023Article
- Fluorescent Probes for Mammalian Thioredoxin Reductase: Mechanistic Analysis, Construction Strategies, and Future Perspectives.Biosensors · 2023Review
- Crystal Structure of Histone Deacetylase 6 Complexed with (bioRxiv : the preprint server for biology · 2023Article
- Chemoproteomic target deconvolution reveals Histone Deacetylases as targets of (R)-lipoic acid.Nature communications · 2023Article
- Cyclic Dichalcogenides Extend the Reach of Bioreductive Prodrugs to Harness Thiol/Disulfide Oxidoreductases: Applications toACS central science · 2023Article
- Article
- Thiol-Mediated Uptake.JACS Au · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cyclic five-membered disulfide 1,2-dithiolane has been widely used in chemical biology and in redox probes. Contradictory reports have described it either as nonspecifically reduced in cells, or else as a highly specific substrate for thioredoxin reductase (TrxR). Here we show that 1,2-dithiolane probes, such as "TRFS" probes, are nonspecifically reduced by thiol reductants and redox-active proteins, and their cellular performance is barely affected by TrxR inhibition or knockout. Therefore, results of cellular imaging or inhibitor screening using 1,2-dithiolanes should not be interpreted as reflecting TrxR activity, and previous studies may need re-evaluation. To understand 1,2-dithiolanes' complex behaviour, probe localisation, environment-dependent fluorescence, reduction-independent ring-opening polymerisation, and thiol-dependent cellular uptake must all be considered; particular caution is needed when co-applying thiophilic inhibitors. We present a general approach controlling against assay misinterpretation with reducible probes, to ensure future TrxR-targeted designs are robustly evaluated for selectivity, and to better orient future research.
Indexed as
Identifiers
What OpenQuestion holds
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.