Evidence map›Paper›PMID 41310159›Full record

ArticleCommunications chemistry2025

Fragment-based drug design of a bacterial kinase inhibitor capable of increasing the antibiotic sensitivity of clinical isolates.

Julien Kowalewski, Robin Deutscher, Marion Richardoz, Mathilde Tomaszczyk, Muriel Gelin, Gilles Labesse, Felix Hausch, Gerard D Wright, Catherine Dunyach-Remy, Jean-François Guichou and 1 more

Abstract read
In one paragraph

Article in Communications chemistry, 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. Article
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.

Julien KowalewskiCentre de Biologie Structurale (CBS), University of Montpellier, CNRS UMR 5048, INSERM U1054, Montpellier, France.ORCID http://orcid.org/0009-0005-4042-8145
Robin DeutscherInstitute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Darmstadt, Germany.
Marion RichardozVirulence Bactérienne et Infections Chroniques, INSERM U1047, Department of Microbiology and Hospital Hygiene, University of Montpellier, Nîmes, France.
Mathilde TomaszczykCentre de Biologie Structurale (CBS), University of Montpellier, CNRS UMR 5048, INSERM U1054, Montpellier, France.
Muriel GelinCentre de Biologie Structurale (CBS), University of Montpellier, CNRS UMR 5048, INSERM U1054, Montpellier, France.
Gilles LabesseCentre de Biologie Structurale (CBS), University of Montpellier, CNRS UMR 5048, INSERM U1054, Montpellier, France.
Felix HauschInstitute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Darmstadt, Germany.ORCID http://orcid.org/0000-0002-3710-8838
Gerard D WrightM.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.ORCID http://orcid.org/0000-0002-9129-7131
Catherine Dunyach-RemyVirulence Bactérienne et Infections Chroniques, INSERM U1047, Department of Microbiology and Hospital Hygiene, University of Montpellier, Nîmes, France.
Jean-François GuichouCentre de Biologie Structurale (CBS), University of Montpellier, CNRS UMR 5048, INSERM U1054, Montpellier, France.
Corinne LionneCentre de Biologie Structurale (CBS), University of Montpellier, CNRS UMR 5048, INSERM U1054, Montpellier, France. corinne.lionne@cnrs.fr.ORCID http://orcid.org/0000-0002-6348-5311

Funding

Agence Nationale de la Recherche (French National Research Agency) ANR-10-INBS-0004Agence Nationale de la Recherche (French National Research Agency) ANR-10-INBS-0005Agence Nationale de la Recherche (French National Research Agency) ANR-19-AMRB-0001Association Vaincre la Mucoviscidose (Vaincre la Mucoviscidos) RF20220503015Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01KI2126BGouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) FDN148463Mitacs NA
6 · The paper itself

Abstract

According to the World Health Organization (WHO), antimicrobial resistance is a serious global health issue. Overcoming antibiotic resistance involves several strategies, including the inhibition of resistance mechanisms. Among the various resistance mechanisms, aminoglycoside phosphotransferases (APHs) catalyze the transfer of the γ-phosphate from a nucleotide donor to various aminoglycosides, leading to their inactivation. In this work, using a fragment-based drug design (FBDD) approach, we have identified and characterized a promising APH inhibitor capable of increasing the sensitivity of Pseudomonas aeruginosa and Staphylococcus aureus resistant to aminoglycosides. It is therefore a good candidate for the future development of APH inhibitors to be prescribed in combination with aminoglycosides. This molecule is a competitive inhibitor of adenosine 5'-triphosphate (ATP), the phosphate donor of APHs. Further studies are required to optimize this molecule to improve its specificity for APHs and its bioavailability in bacteria.

Identifiers

PMID41310159
PMCPMC12749166

What OpenQuestion holds

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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.