Evidence map›Paper›PMID 41946736›Full record

ArticleNature communications2026

Alpibectir-Ethionamide combination (AlpE) for the treatment of tuberculosis.

Zainab Edoo, Camille Grosse, Thomas Maitre, Rosangela Frita, Aurélie Chauffour, Laure Fournier Le Ray, Alexandre Godmer, Alexandra Aubry, Marilyne Bourotte, Rudy Antoine and 28 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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

38 authors.

Zainab Edoo *Univ. Lille, CNRS, Inserm, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France.
Camille Grosse *Univ. Lille, CNRS, Inserm, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France.
Thomas Maitre *Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI, F-75013, Paris, France.
Rosangela Frita *Univ. Lille, CNRS, Inserm, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France.
Aurélie ChauffourSorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI, F-75013, Paris, France.ORCID http://orcid.org/0000-0002-8846-5069
Laure Fournier Le RaySorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI, F-75013, Paris, France.
Alexandre GodmerSorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI, F-75013, Paris, France.ORCID http://orcid.org/0000-0002-5211-5796
Alexandra AubrySorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI, F-75013, Paris, France.
Marilyne BourotteBioVersys SAS, Lille, France.
Rudy AntoineUniv. Lille, CNRS, Inserm, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France.ORCID http://orcid.org/0000-0002-7369-0626
Lina TawkUniv. Lille, CNRS, Inserm, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France.
Stéphanie SlupekUniv. Lille, CNRS, Inserm, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France.
Vincent TreboscBioVersys AG, Basel, Switzerland.ORCID http://orcid.org/0000-0002-8961-1371
Birgit SchellhornBioVersys AG, Basel, Switzerland.
Aurore DreneauBioVersys SAS, Lille, France.
Line HofmannBioVersys SAS, Lille, France.
Christian KemmerBioVersys AG, Basel, Switzerland.
Sergio LociuroBioVersys SAS, Lille, France.
Glenn E DaleBioVersys SAS, Lille, France.
Françoise JungBioVersys AG, Basel, Switzerland.ORCID http://orcid.org/0009-0002-2731-0327
Esther Pérez-HerránGSK, Tres Cantos R&D, PTM, Tres Cantos, Madrid, Spain.ORCID http://orcid.org/0000-0002-4464-9528
Alfonso MendozaGSK, Tres Cantos R&D, PTM, Tres Cantos, Madrid, Spain.ORCID http://orcid.org/0000-0003-2493-4118
Maria Jose Rebollo LópezGSK, Tres Cantos R&D, PTM, Tres Cantos, Madrid, Spain.
Sonja Ghidelli-DisseCellzome GmbH. A GSK Company, Heidelberg, Germany.
Thilo WernerCellzome GmbH. A GSK Company, Heidelberg, Germany.
Lluis BallellGSK, Tres Cantos R&D, PTM, Tres Cantos, Madrid, Spain.
David Barros-AguirreGSK, Tres Cantos R&D, PTM, Tres Cantos, Madrid, Spain.ORCID http://orcid.org/0000-0002-4099-0438
Vanessa MathysNational Reference Center for Tuberculosis and Mycobacteria, Sciensano, Brussels, Belgium.ORCID http://orcid.org/0000-0001-5218-927X
Karine SoetaertNational Reference Center for Tuberculosis and Mycobacteria, Sciensano, Brussels, Belgium.
Véronique MegalizziResearch Department in Drug Development, Faculty of Pharmacy, Université Libre de Bruxelles, ULB, Bruxelles, Belgium.
René WintjensResearch Department in Drug Development, Faculty of Pharmacy, Université Libre de Bruxelles, ULB, Bruxelles, Belgium.ORCID http://orcid.org/0000-0002-0234-7847
Marc GitzingerBioVersys SAS, Lille, France.
Benoit DeprezUniv. Lille, Inserm, Institut Pasteur de Lille, U1177 - Drugs and Molecules for Living Systems, Lille, France.ORCID http://orcid.org/0000-0002-2777-4538
Nicolas VezirisSorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI, F-75013, Paris, France.
Modesto J RemuiñánGSK, Tres Cantos R&D, PTM, Tres Cantos, Madrid, Spain.
Nicolas WillandUniv. Lille, Inserm, Institut Pasteur de Lille, U1177 - Drugs and Molecules for Living Systems, Lille, France. nicolas.willand@univ-lille.fr.
Michel PierenBioVersys AG, Basel, Switzerland. michel.pieren@bioversys.com.
Alain R BaulardUniv. Lille, CNRS, Inserm, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France. alain.baulard@pasteur-lille.fr.ORCID http://orcid.org/0000-0002-0150-5241

Funding

Agence Nationale de la Recherche (French National Research Agency) Mustart ANR-20-PAMR-0005Innovative Medicines Initiative (IMI) 853800Région Hauts-de-France 2108838
6 · The paper itself

Abstract

Ethionamide (Eto) and prothionamide (Pto) are second-line antibiotics used for tuberculosis (TB) treatment. Both are prodrugs whose antibacterial activity depends on bioactivation by oxidases in Mycobacterium tuberculosis, including the Baeyer-Villiger monooxygenase MymA. Through biophysical, genetic, and cellular assays, we show that the clinical candidate alpibectir (Alp, BVL-GSK098) binds the transcriptional regulator VirS, increasing MymA expression and potentiating Eto and Pto activity. Alpibectir also boosts the activity of the corresponding host-derived sulfoxide metabolites. We additionally show that alpibectir exhibits intrinsic antibacterial activity via overexpression of the mymA operon. The alpibectir/Eto (AlpE) combination is rapidly bactericidal in vitro and in mice, lowers the frequency of spontaneous resistance of Eto, and remains active on Eto- and isoniazid-resistant strains, including isolates with inhA promoter mutations. Alpibectir was safe in a Phase 1 human clinical trial. Together with the potentiation data presented here, these findings highlight its potential to optimize TB chemotherapy by reducing Eto/Pto doses, which can minimize dose-related side effects, enhancing adherence.

Indexed as

Antitubercular AgentsEthionamideMycobacterium tuberculosisTuberculosisAnimalsBacterial ProteinsDrug Resistance, BacterialFemaleHumansMiceMicrobial Sensitivity TestsMixed Function OxygenasesOxidoreductasesAntitubercular AgentsBacterial ProteinsEthionamideMixed Function OxygenasesOxidoreductases

Identifiers

PMID41946736
PMCPMC13234193

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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.