Evidence map›Paper›PMID 35612562›Full record

ArticleAngewandte Chemie (International ed. in English)2022

Small Molecule Inhibitors of Interferon-Induced JAK-STAT Signalling.

Leishemba K Thoidingjam, Cédric M Blouin, Christine Gaillet, Aurélien Brion, Stéphanie Solier, Supaporn Niyomchon, Ahmed El Marjou, Sara Mouasni, Fernando E Sepulveda, Geneviève de Saint Basile and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Small Molecule Inhibitors of Interferon-Induced JAK-STAT Signalling.Angewandte Chemie (International ed. in English) · 2022
    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

12 authors at 3 institutions in 1 country.

Leishemba K ThoidingjamChemical Biology Laboratory, Institut Curie, PSL Research University, CNRS UMR 3666, INSERM U1143, 75005, Paris, France.ORCID 0000-0002-4549-5153
Cédric M BlouinMembrane Mechanics and Dynamics of Intracellular Signalling, Institut Curie, PSL Research University, CNRS UMR 3666, INSERM U1143, 75005, Paris, France.ORCID 0000-0003-0800-0948
Christine GailletChemical Biology Laboratory, Institut Curie, PSL Research University, CNRS UMR 3666, INSERM U1143, 75005, Paris, France.ORCID 0000-0002-1208-1130
Aurélien BrionChemical Biology Laboratory, Institut Curie, PSL Research University, CNRS UMR 3666, INSERM U1143, 75005, Paris, France.ORCID 0000-0002-4686-5865
Stéphanie SolierChemical Biology Laboratory, Institut Curie, PSL Research University, CNRS UMR 3666, INSERM U1143, 75005, Paris, France.ORCID 0000-0003-3867-4644
Supaporn NiyomchonChemical Biology Laboratory, Institut Curie, PSL Research University, CNRS UMR 3666, INSERM U1143, 75005, Paris, France.
Ahmed El MarjouProtein Expression and Purification Core Facility, Institut Curie, PSL Research University, UMR 144 CNRS, 75005, Paris, France.ORCID 0000-0002-0149-428X
Sara MouasniMolecular basis of altered immune homeostasis laboratory, Université de Paris, Imagine Institute, INSERM UMR 1163, 75015, Paris, France.ORCID 0000-0002-1264-2225
Fernando E SepulvedaMolecular basis of altered immune homeostasis laboratory, Université de Paris, Imagine Institute, INSERM UMR 1163, 75015, Paris, France.ORCID 0000-0001-5865-4929
Geneviève de Saint BasileMolecular basis of altered immune homeostasis laboratory, Université de Paris, Imagine Institute, INSERM UMR 1163, 75015, Paris, France.ORCID 0000-0002-1913-5269
Christophe LamazeMembrane Mechanics and Dynamics of Intracellular Signalling, Institut Curie, PSL Research University, CNRS UMR 3666, INSERM U1143, 75005, Paris, France.ORCID 0000-0001-5430-2707
Raphaël RodriguezChemical Biology Laboratory, Institut Curie, PSL Research University, CNRS UMR 3666, INSERM U1143, 75005, Paris, France.ORCID 0000-0001-7668-446X
Centre National de la Recherche Scientifique · FRInserm · FRHôpital Necker-Enfants Malades · FR

Funding

European Research Council 647973
6 · The paper itself

Abstract

Interferons (IFN) are cytokines which, upon binding to cell surface receptors, trigger a series of downstream biochemical events including Janus Kinase (JAK) activation, phosphorylation of Signal Transducer and Activator of Transcription protein (STAT), translocation of pSTAT to the nucleus and transcriptional activation. Dysregulated IFN signalling has been linked to cancer progression and auto-immune diseases. Here, we report the serendipitous discovery of a small molecule that blocks IFNγ activation of JAK-STAT signalling. Further lead optimisation gave rise to a potent and more selective analogue that exerts its activity by a mechanism consistent with direct IFNγ targeting in vitro, which reduces bleeding in model of haemorrhagic colitis in vivo. This first-in-class small molecule also inhibits type I and III IFN-induced STAT phosphorylation in vitro. Our work provides the basis for the development of pan-IFN inhibitory drugs.

Indexed as

InterferonsJanus KinasesInterferon-gammaPhosphorylationSignal TransductionInterferon-gammaInterferonsJanus KinasesForminInterferonJAK-STAT SignallingSmall MoleculeSMIFH2

Identifiers

PMID35612562
PMCPMC9400964
OpenAlexW4281490178

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.