ArticleNature communications2021
Structural insights into the disruption of TNF-TNFR1 signalling by small molecules stabilising a distorted TNF.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 84 citations in OpenAlex.
- Phase 1 study of balinatunfib, an oral inhibitor of TNFR1 signal in mild-to-moderate psoriasis.Journal of the European Academy of Dermatology and Venereology : JEADV · 2026Trial
- Realizing the potential of agonistic antibody immunotherapy.Nature reviews. Drug discovery · 2026Review
- HDX-MS Detects Steric Protection and Trimeric Compaction of TNFα after It Binds Receptors or Antibodies.ACS omega · 2026Article
- Soluble tumor necrosis factor receptors in diabetes: risk sensing and receptor-resolved targeting.Endocrine journal · 2026Review
- Discovery of Ligands for the TNFR1 Extracellular Domain Using Fragment-Based Drug Discovery.ChemMedChem · 2026Article
- Molecular determinants of TNFR1:TNFα binding and dynamics in a physiological membrane environment.Current research in structural biology · 2026Article
- Integrated network pharmacology and experimental validation to elucidate the mechanism of Lysimachia paridiformis var. stenophylla Franch. in rheumatoid arthritis.Scientific reports · 2026Article
- Promising TNF-α inhibitors: Targeting pathogenic TNF-α/TNFR signaling to restore Th17/Treg balance in rheumatoid arthritis.Journal of pharmaceutical analysis · 2026Review
- Icariin-mediated structural stabilization of TNF-α triggers a pro-regenerative signaling switch for endothelial recovery after myocardial infarction.Frontiers in pharmacology · 2026Article
- Immunization with detoxified TNFα elicits neutralizing antibodies and ameliorates inflammatory shock and autoimmune arthritis in mice.Frontiers in immunology · 2026Article
- The importance of TNF-α signaling: a potential risk factor in neurodegenerative and cardiovascular diseases.Archives of medical science : AMS · 2026Article
- Anacardic acid ameliorates insulin resistance and diabetic nephropathy: network pharmacology, in vivo and molecular docking studies targeting TNF- α / TGFβR1 signaling.Journal of natural medicines · 2025Article
- Key Signals Produced by Gut Microbiota Associated with Metabolic Syndrome, Cancer, Cardiovascular Diseases, and Brain Functions.International journal of molecular sciences · 2025Review
- Hybrid Receptor-Mediated Molecular Delineations in TNF-α and IGF-1-Induced Costimulatory Effects.International journal of molecular sciences · 2025Article
- Balinatunfib: A Clinical Oral Small Molecule TNFα Inhibitor.ChemMedChem · 2025Article
- Highly ordered clustering of TNFα and BAFF ligand-receptor-intracellular adaptor complexes on a lipid membrane.Nature communications · 2025Article
- The Role of Inflammatory Markers in Linking Metabolic Syndrome to Cognitive Decline in Middle-Aged Women: A Focus on TNF-α and IL-6.Metabolites · 2025Article
- Exploring TNFR1: from discovery to targeted therapy development.Journal of translational medicine · 2025Review
- ExploringJournal of inflammation research · 2025Article
- Unraveling the Therapeutic Potential ofCurrent pharmaceutical design · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumour necrosis factor (TNF) is a trimeric protein which signals through two membrane receptors, TNFR1 and TNFR2. Previously, we identified small molecules that inhibit human TNF by stabilising a distorted trimer and reduce the number of receptors bound to TNF from three to two. Here we present a biochemical and structural characterisation of the small molecule-stabilised TNF-TNFR1 complex, providing insights into how a distorted TNF trimer can alter signalling function. We demonstrate that the inhibitors reduce the binding affinity of TNF to the third TNFR1 molecule. In support of this, we show by X-ray crystallography that the inhibitor-bound, distorted, TNF trimer forms a complex with a dimer of TNFR1 molecules. This observation, along with data from a solution-based network assembly assay, leads us to suggest a model for TNF signalling based on TNF-TNFR1 clusters, which are disrupted by small molecule inhibitors.
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Registered trials
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.