Evidence map›Paper›PMID 41550929›Full record

ArticleFrontiers in immunology2025

STING activation by teniposide: a potential direct mechanism beyond cGAS stimulation.

Javier Arranz-Herrero, Laura Marquez-Cantudo, Sergio Rius-Rocabert, Rubén M Buey, Adrian Velazquez-Campoy, Vicent Tur-Planells, Adolfo Garcia-Sastre, Lisa Miorin, Beatriz de Pascual-Teresa, Claire Coderch and 1 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

11 authors.

Javier Arranz-HerreroMicrobiology Section, Departamento de Ciencias, Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain.
Laura Marquez-CantudoDepartamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain.
Sergio Rius-RocabertMicrobiology Section, Departamento de Ciencias, Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain.
Rubén M BueyMetabolic Engineering Group - Unit Associated to CSIC through IRNASA, Department of Microbiology and Genetics, Universidad de Salamanca, Salamanca, Spain.
Adrian Velazquez-CampoyInstitute of Biocomputation and Physics of Complex Systems (BIFI), Universidad de Zaragoza, Zaragoza, Spain.
Vicent Tur-PlanellsMicrobiology Section, Departamento de Ciencias, Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain.
Adolfo Garcia-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Lisa MiorinDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Beatriz de Pascual-TeresaDepartamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain.
Claire CoderchDepartamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain.
Estanislao Nistal-VillanMicrobiology Section, Departamento de Ciencias, Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain.

Funding

Supplement: Adjuvant Screening for an inactivated SFTSV Vaccine75N93019C00046 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ADOLFO, GARCIA-SASTRE · 2019 to 2023
$9.1M
NIAID NIH HHS 75N93019C00046
6 · The paper itself

Abstract

Introduction: The STimulator of Interferon Genes (STING) is a key adaptor protein in the innate immune response to cytosolic DNA, making it a promising therapeutic target. Identifying novel STING ligands could provide new opportunities for immune modulation. Methods: We employed high-throughput virtual screening to identify potential STING ligands and selected Teniposide, an anticancer drug primarily used for infant leukemia. Direct binding of Teniposide to STING's cytosolic domain was confirmed via isothermal titration calorimetry (ITC) and validated using a double mutant STING variant unable to bind Teniposide. Computational docking and molecular dynamics simulations were performed to characterize the binding mode. Results: Teniposide activated the IFN-β signaling pathway in a STING-dependent manner, independent of dsDNA sensors cyclic GMP-AMP synthase (cGAS) and Interferon Gamma Inducible Protein 16 (IFI16). ITC confirmed direct interaction, and the STING double mutant abolished binding. Computational analyses revealed a symmetrical binding mode involving two Teniposide molecules interacting with STING. Discussion: These findings suggest that Teniposide activates STING through a previously unrecognized, cGAS-independent mechanism, while retaining potential for canonical cGAS-STING stimulation. Our combined computational and experimental evidence supports repurposing Teniposide as a STING agonist, highlighting new therapeutic possibilities for innate immune stimulation.

Indexed as

Membrane ProteinsNucleotidyltransferasesAnimalscGAS-STING Signaling PathwayCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseHEK293 CellsHumansImmunity, InnateInterferon-betaLigandsMolecular Docking SimulationMolecular Dynamics SimulationProtein BindingSignal TransductionSTING ProteincGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseInterferon-betaLigandsMembrane ProteinsNucleotidyltransferasesSTING1 protein, humanSTING ProteinCyclic dinucleotides (CDNs)High-throughput virtual screening (HTVS)IFN-βImmunotherapy drug repurposingIsothermal titration calorimetry (ITC)Molecular dockingSTINGTeniposide

Identifiers

PMID41550929
PMCPMC12808447

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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.