Evidence map›Paper›PMID 41759308›Full record

ArticleEuropean journal of medicinal chemistry2026

Dual-action mitochondria-targeted prodrugs that both deplete mitochondrial glutathione and deliver a toxic payload to the matrix.

Patrick A Cardwell, Alva M Casey, Suvagata Roy Chowdhury, Eloïse Marques, Chak Shun Yu, Rebecca L Taig, Stuart T Caldwell, Julien Prudent, Michael P Murphy, Richard C Hartley

Abstract read
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In one paragraph

Article in European journal of medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Patrick A CardwellSchool of Chemistry, Joseph Black Building, University Avenue, University of Glasgow, Glasgow, G12 8QQ, UK; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
Alva M CaseyMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
Suvagata Roy ChowdhuryMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
Eloïse MarquesMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
Chak Shun YuMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
Rebecca L TaigSchool of Chemistry, Joseph Black Building, University Avenue, University of Glasgow, Glasgow, G12 8QQ, UK.
Stuart T CaldwellSchool of Chemistry, Joseph Black Building, University Avenue, University of Glasgow, Glasgow, G12 8QQ, UK.
Julien PrudentMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
Michael P MurphyMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK; Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK. Electronic address: mpm37@cam.ac.uk.
Richard C HartleySchool of Chemistry, Joseph Black Building, University Avenue, University of Glasgow, Glasgow, G12 8QQ, UK. Electronic address: richard.hartley@glasgow.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mitochondrial glutathione (mGSH) protects the organelle and the cell against reactive oxygen species (ROS), electrophilic metabolites and xenobiotics. Many cancers upregulate GSH to confer resistance against cell death by ferroptosis and anticancer drugs, so mGSH depletion is a potential anticancer strategy. We previously developed MitoCDNB, a mitochondria-targeted molecule that selectively depletes mGSH and disrupts mitochondrial thiol redox homeostasis. However, mGSH depletion by MitoCDNB required catalysis by glutathione-S-transferases (GSTs). Here, we develop a dual-action prodrug scaffold to deplete mGSH independently of GSTs and simultaneously release a payload to increase oxidative stress. The scaffold has four components: a triphenylphosphonium (TPP) group for targeting to the mitochondria, a GSH-reactive electrophilic dinitroaryl ring bearing a sulfonamide leaving group for depleting mGSH, an ethylenediamine-derived self-immolative linker and a phenolic payload. The rates of nucleophilic aromatic substitution (S

Indexed as

Antineoplastic AgentsGlutathioneMitochondriaProdrugsDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansMolecular StructureOrganophosphorus CompoundsOxidative StressReactive Oxygen SpeciesStructure-Activity RelationshipAntineoplastic AgentsGlutathioneOrganophosphorus CompoundsProdrugsReactive Oxygen SpeciesCancerGlutathioneMitochondriaOxidative stressProdrugReactive oxygen species

Identifiers

PMID41759308
PMCPMC13201212

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Registered trials

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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.