Evidence map›Paper›PMID 42399717›Full record

ArticleChemMedChem2026

Discovery of Ligands for the TNFR1 Extracellular Domain Using Fragment-Based Drug Discovery.

Henri Chédotal, Katrine Povlsen, Dilip Narayanan, Charlotte H Gotfredsen, Michael Gajhede, Anders Bach, Mads H Clausen

Abstract read
In one paragraph

Article in ChemMedChem, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Henri ChédotalDepartment of Chemistry, Technical University of Denmark, Kgs. Lyngby, Denmark.ORCID https://orcid.org/0000-0002-6342-624X
Katrine PovlsenDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Dilip NarayananDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Charlotte H GotfredsenDepartment of Chemistry, Technical University of Denmark, Kgs. Lyngby, Denmark.
Michael GajhedeDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Anders BachDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID https://orcid.org/0000-0003-4305-9910
Mads H ClausenDepartment of Chemistry, Technical University of Denmark, Kgs. Lyngby, Denmark.ORCID https://orcid.org/0000-0001-9649-1729

Funding

Carlsbergfondet CF19-0072Danmarks Frie Forskningsfond 1032-00084BNovo Nordisk Fonden NNF19OC0055818Svenska Forskningsrådet Formas 2019-02496Vetenskapsrådet 2018-07152Villum FondenVINNOVA 2018-04969
6 · The paper itself

Abstract

Tumor necrosis factor receptor 1 (TNFR1) plays a major role in immunoregulation. It is involved in inflammatory and autoimmune diseases like rheumatoid arthritis, psoriasis, Alzheimer's disease, and multiple sclerosis. However, few small-molecule inhibitors of TNFR1 have been reported, even though they constitute a good alternative to already existing antibody therapies targeting the TNF pathway. Here, we report the discovery of a new class of molecules for the extracellular domain of TNFR1 using a fragment-based approach through primary screening by NMR spectroscopy, followed by orthogonal validation by surface plasmon resonance (SPR) and X-ray crystallography. Guided by these results, we have synthesized 46 analogs with micromolar potency showing up to ∼10-fold improved affinity toward TNFR1 compared to the fragment hits. These results can provide a structural basis for the discovery of novel TNFR1 inhibitors in the future.

Indexed as

Drug DiscoveryReceptors, Tumor Necrosis Factor, Type ISmall Molecule LibrariesCrystallography, X-RayDose-Response Relationship, DrugHumansLigandsModels, MolecularMolecular StructureProtein DomainsStructure-Activity RelationshipSurface Plasmon ResonanceLigandsReceptors, Tumor Necrosis Factor, Type ISmall Molecule Librariesfragment‐based screeningNMRprotein crystallographySPRTNFR1

Identifiers

PMID42399717
PMCPMC13331996

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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.