Evidence map›Paper›PMID 28566766›Full record

ArticleScientific reports2017

Identification of a small molecule that primes the type I interferon response to cytosolic DNA.

Samira Khiar, Marianne Lucas-Hourani, Sébastien Nisole, Nikaïa Smith, Olivier Helynck, Maryline Bourgine, Claude Ruffié, Jean-Philippe Herbeuval, Hélène Munier-Lehmann, Frédéric Tangy and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-weighted citation impact, top 26% of its field
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

9 citing papers in PubMed, 17 citations in OpenAlex.

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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 at 3 institutions in 1 country.

Samira KhiarUnité de Génomique Virale et Vaccination, Institut Pasteur, CNRS UMR3569, Paris, France.
Marianne Lucas-HouraniUnité de Génomique Virale et Vaccination, Institut Pasteur, CNRS UMR3569, Paris, France.
Sébastien NisoleMécanismes d'action des interférons et voies bio-thérapeutiques, Université Paris Descartes, INSERM UMR-S1124, Paris, France.ORCID 0000-0001-9793-419X
Nikaïa SmithChimie & Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS UMR8601, Paris, France.ORCID 0000-0002-0202-612X
Olivier HelynckUnité de Chimie et Biocatalyse, Institut Pasteur, CNRS UMR3523, Paris, France.
Maryline BourgineUnité de Virologie Moléculaire et Vaccinologie, Institut Pasteur, Paris, France.
Claude RuffiéUnité de Génomique Virale et Vaccination, Institut Pasteur, CNRS UMR3569, Paris, France.
Jean-Philippe HerbeuvalChimie & Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS UMR8601, Paris, France.
Hélène Munier-LehmannUnité de Chimie et Biocatalyse, Institut Pasteur, CNRS UMR3523, Paris, France.
Frédéric TangyUnité de Génomique Virale et Vaccination, Institut Pasteur, CNRS UMR3569, Paris, France. ftangy@pasteur.fr.
Pierre-Olivier VidalainChimie & Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS UMR8601, Paris, France. pierre-olivier.vidalain@parisdescartes.fr.
Centre National de la Recherche Scientifique · FRDélégation Paris 5 · FRInstitut Pasteur · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The type I interferon response plays a pivotal role in host defense against infectious agents and tumors, and promising therapeutic approaches rely on small molecules designed to boost this system. To identify such compounds, we developed a high-throughput screening assay based on HEK-293 cells expressing luciferase under the control of Interferon-Stimulated Response Elements (ISRE). An original library of 10,000 synthetic compounds was screened, and we identified a series of 1H-benzimidazole-4-carboxamide compounds inducing the ISRE promoter sequence, specific cellular Interferon-Stimulated Genes (ISGs), and the phosphorylation of Interferon Regulatory Factor (IRF) 3. ISRE induction by ChX710, a prototypical member of this chemical series, was dependent on the adaptor MAVS and IRF1, but was IRF3 independent. Although it was unable to trigger type I IFN secretion per se, ChX710 efficiently primed cellular response to transfected plasmid DNA as assessed by potent synergistic effects on IFN-β secretion and ISG expression levels. This cellular response was dependent on STING, a key adaptor involved in the sensing of cytosolic DNA and immune activation by various pathogens, stress signals and tumorigenesis. Our results demonstrate that cellular response to cytosolic DNA can be boosted with a small molecule, and potential applications in antimicrobial and cancer therapies are discussed.

Indexed as

High-Throughput Screening AssaysCytosolDNAGene Expression RegulationHEK293 CellsHumansInterferon Regulatory Factor-3Interferon Type IPromoter Regions, GeneticResponse ElementsSmall Molecule LibrariesTransfectionDNAInterferon Regulatory Factor-3Interferon Type IIRF3 protein, humanSmall Molecule Libraries

Identifiers

PMID28566766
PMCPMC5451460
OpenAlexW2610029107

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.