Evidence map›Paper›PMID 38877290›Full record

ArticleEMBO molecular medicine2024

Disrupting TSLP-TSLP receptor interactions via putative small molecule inhibitors yields a novel and efficient treatment option for atopic diseases.

Partho Protim Adhikary, Temilolu Idowu, Zheng Tan, Christopher Hoang, Selina Shanta, Malti Dumbani, Leah Mappalakayil, Bhuwan Awasthi, Marcel Bermudez, January Weiner and 4 more

Erratum issuedAbstract read
In one paragraph

Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–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

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Efficacy of tezepelumab in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
    Pooled it
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Partho Protim AdhikaryFaculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0002-3755-0810
Temilolu IdowuFaculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0003-1583-8562
Zheng TanFaculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.
Christopher HoangFaculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.
Selina ShantaFaculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.
Malti DumbaniInstitute of Pharmacy, Freie Universität of Berlin, Berlin, Germany.
Leah MappalakayilFaculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.ORCID http://orcid.org/0009-0009-7418-1215
Bhuwan AwasthiFaculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0002-2636-510X
Marcel BermudezInstitute of Pharmacy, Freie Universität of Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-7421-3282
January WeinerBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Germany Charité - Universitätsmedizin Berlin, Berlin, Germany.
Dieter BeuleBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Germany Charité - Universitätsmedizin Berlin, Berlin, Germany.
Gerhard WolberInstitute of Pharmacy, Freie Universität of Berlin, Berlin, Germany.
Brent Dg PageFaculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada. brent.page@ubc.ca.ORCID http://orcid.org/0000-0002-2101-1329
Sarah HedtrichFaculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada. sarah.hedtrich@bih-charite.de.ORCID http://orcid.org/0000-0001-6770-3657

Funding

Canadian Government | Canadian Institutes of Health Research (CIHR) AWD-016113 CIHR 2020
6 · The paper itself

Abstract

Thymic stromal lymphopoietin (TSLP) is a key player in atopic diseases, which has sparked great interest in therapeutically targeting TSLP. Yet, no small-molecule TSLP inhibitors exist due to the challenges of disrupting the protein-protein interaction between TSLP and its receptor. Here, we report the development of small-molecule TSLP receptor inhibitors using virtual screening and docking of >1,000,000 compounds followed by iterative chemical synthesis. BP79 emerged as our lead compound that effectively abrogates TSLP-triggered cytokines at low micromolar concentrations. For in-depth analysis, we developed a human atopic disease drug discovery platform using multi-organ chips. Here, topical application of BP79 onto atopic skin models that were co-cultivated with lung models and Th2 cells effectively suppressed immune cell infiltration and IL-13, IL-4, TSLP, and periostin secretion, while upregulating skin barrier proteins. RNA-Seq analysis corroborate these findings and indicate protective downstream effects on the lungs. To the best of our knowledge, this represents the first report of a potent putative small molecule TSLPR inhibitor which has the potential to expand the therapeutic and preventive options in atopic diseases.

Indexed as

CytokinesReceptors, CytokineThymic Stromal LymphopoietinAnimalsDermatitis, AtopicHumansInterleukin-4LungMolecular Docking SimulationProtein BindingSkinSmall Molecule LibrariesTh2 CellsCRLF2 protein, humanCytokinesInterleukin-4Receptors, CytokineSmall Molecule LibrariesThymic Stromal LymphopoietinTSLP protein, humanAtopic DermatitisAtopic DiseasesOrgan-on-chipSmall Molecule InhibitorTSLP

Identifiers

PMID38877290
PMCPMC11250841

What OpenQuestion holds

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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.