Evidence map›Paper›PMID 39821709›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Humanized Candida and NanoBiT Assays Expedite Discovery of Bdf1 Bromodomain Inhibitors With Antifungal Potential.

Kaiyao Wei, Marie Arlotto, Justin M Overhulse, Tuan-Anh Dinh, Yingsheng Zhou, Nathan J Dupper, Jiayi Yang, Boris A Kashemirov, Hasan Dawi, Cécile Garnaud and 13 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

23 authors.

Kaiyao WeiUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, 38000, France.
Marie ArlottoUniv. Grenoble Alpes, Inserm, CNRS, Institute for Advanced Biosciences (IAB), Grenoble, 38000, France.
Justin M OverhulseDepartment of Chemistry, Dana and David Dornsife College of Letters, Arts, and Sciences, University of Southern California, University Park Campus, Los Angeles, CA, 90089, USA.
Tuan-Anh DinhUniv. Grenoble Alpes, CNRS, Grenoble INP, CHU Grenoble Alpes, Laboratoire TIMC, Grenoble, 38000, France.
Yingsheng ZhouDepartment of Chemistry, Dana and David Dornsife College of Letters, Arts, and Sciences, University of Southern California, University Park Campus, Los Angeles, CA, 90089, USA.
Nathan J DupperDepartment of Chemistry, Dana and David Dornsife College of Letters, Arts, and Sciences, University of Southern California, University Park Campus, Los Angeles, CA, 90089, USA.
Jiayi YangDepartment of Chemistry, Dana and David Dornsife College of Letters, Arts, and Sciences, University of Southern California, University Park Campus, Los Angeles, CA, 90089, USA.
Boris A KashemirovDepartment of Chemistry, Dana and David Dornsife College of Letters, Arts, and Sciences, University of Southern California, University Park Campus, Los Angeles, CA, 90089, USA.
Hasan DawiUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, 38000, France.
Cécile GarnaudUniv. Grenoble Alpes, CNRS, Grenoble INP, CHU Grenoble Alpes, Laboratoire TIMC, Grenoble, 38000, France.
Gaëlle BourgineUniv. Rennes, CNRS, INSERM, Institut de Génétique et Développement de Rennes (IGDR), UMR 6290, U1305, Rennes, 35000, France.
Flore MiettonUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, 38000, France.
Morgane ChamplebouxUniv. Grenoble Alpes, Inserm, CNRS, Institute for Advanced Biosciences (IAB), Grenoble, 38000, France.
Amédé LarabiUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, 38000, France.
Yordan HayatUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, 38000, France.
Rose-Laure IndoratoUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, 38000, France.
Marjolaine Noirclerc-SavoyeUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, 38000, France.
Dimitrios SkoufiasUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, 38000, France.
Muriel CornetUniv. Grenoble Alpes, CNRS, Grenoble INP, CHU Grenoble Alpes, Laboratoire TIMC, Grenoble, 38000, France.
Gwenaël RabutUniv. Rennes, CNRS, INSERM, Institut de Génétique et Développement de Rennes (IGDR), UMR 6290, U1305, Rennes, 35000, France.
Charles E McKennaDepartment of Chemistry, Dana and David Dornsife College of Letters, Arts, and Sciences, University of Southern California, University Park Campus, Los Angeles, CA, 90089, USA.ORCID https://orcid.org/0000-0002-3540-6663
Carlo PetosaUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, 38000, France.ORCID https://orcid.org/0000-0002-9975-1167
Jérôme GovinUniv. Grenoble Alpes, Inserm, CNRS, Institute for Advanced Biosciences (IAB), Grenoble, 38000, France.ORCID https://orcid.org/0000-0001-5511-6965

Funding

Efficient synthon-based modular screening of Giga-to-Terra-scale virtual librariesR01GM147537 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KATRITCH, VSEVOLOD · 2022 to 2024
$1.2M
CBI: Chemistry Biology InterfaceT32GM118289 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FORSBURG, SUSAN L · 2016 to 2020
$1.2M
Agence Nationale de la Recherche ANR-14-CE16-0027Agence Nationale de la Recherche ANR-18-CE18-0007Agence Nationale de la Recherche ANR-21-CE18-0041Commissariat à l'Énergie Atomique et aux Énergies AlternativesFondation Innovations en InfectiologieFondation Innovations en Infectiologie (FINOVI)LABoratoires d'EXcellence GRALNIGMS NIH HHS R01 GM147537NIGMS NIH HHS T32 GM118289NIH HHS GM147537Université Grenoble Alpes
6 · The paper itself

Abstract

The fungal Bromodomain and Extra-Terminal (BET) protein Bdf1 is a potential antifungal target against invasive fungal infections. However, the need to selectively inhibit both Bdf1 bromodomains (BDs) over human orthologs and the lack of molecular tools to assess on-target antifungal efficacy hamper efforts to develop Bdf1 BD inhibitors as antifungal therapeutics. This study reports a phenyltriazine compound that inhibits both Bdf1 BDs from the human fungal pathogen Candida glabrata with selectivity over the orthologous BDs from the human BET protein Brd4. On-target antifungal activity is established by devising two yeast-based inhibition assays: a growth assay using humanized Candida strains in which the Bdf1 BDs are replaced by their Brd4 counterparts, and a NanoBiT assay that evaluates the BD-mediated association of Bdf1 with chromatin. These assays additionally enable the discovery that BET inhibitor I-BET726 targets both Bdf1 BDs, inhibits the growth of a broad spectrum of Candida species, including antifungal-resistant clinical isolates, and displays efficacy in an invertebrate animal model of infection. These collective findings highlight the promising potential of Bdf1 BD inhibitors as an innovative class of antifungal therapeutics and the pivotal role of yeast-based assay development toward achieving this end.

Indexed as

Antifungal AgentsCandidaCandida glabrataFungal ProteinsTranscription FactorsAnimalsDrug DiscoveryHumansAntifungal AgentsFungal ProteinsTranscription FactorsantifungalBdf1BET inhibitionbromodomainCandida

Identifiers

PMID39821709
PMCPMC11904993

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.