ArticleNature communications2019
Small molecules that inhibit TNF signalling by stabilising an asymmetric form of the trimer.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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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.
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Who cites it
61 citing papers in PubMed, 124 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
- First-in-Human Single and Multiple Ascending Dose Studies of Balinatunfib, a Small Molecule Inhibitor of TNFR1 Signaling in Healthy Participants.Clinical pharmacology and therapeutics · 2025Trial
- Intra-cluster receptor density (IRD): A molecular switch for TNFR1 clusters' signaling.Science advances · 2026Article
- Cellular stress triggers degradation and global redistribution of RNAPII.Science advances · 2026Article
- 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
- Network pharmacology refined with non-ubiquity and decoy-controlled molecular docking reveals insights intoFrontiers in bioinformatics · 2026Article
- Icariin-mediated structural stabilization of TNF-α triggers a pro-regenerative signaling switch for endothelial recovery after myocardial infarction.Frontiers in pharmacology · 2026Article
- Elucidating the Mechanism of Xiaoqinglong Decoction in Chronic Urticaria Treatment: An Integrated Approach of Network Pharmacology, Bioinformatics Analysis, Molecular Docking, and Molecular Dynamics Simulations.Current computer-aided drug design · 2026Article
- Exploring the Mechanism of Shexiang Baoxin Pill in the Treatment of Ischemic Stroke: A Study Integrating Network Pharmacology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation.BioMed research international · 2026Article
- Ligand non-competitive GITR antibody prevents formation of the obligatory signal-triggering GITRL: GITR stoichiometry.Scientific reports · 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
- Evaluating the role of 2-hydroxyestradiol in modulating TNF-α signaling and its implications in rheumatoid arthritis.Clinical science (London, England : 1979) · 2025Article
- Bioactive compounds in the modulation of oxidative stress in monocytes and macrophages.Scientific reports · 2025Article
- Article
- Balinatunfib: A Clinical Oral Small Molecule TNFα Inhibitor.ChemMedChem · 2025Article
- Selective CBP/EP300 Bromodomain Inhibitors: Novel Epigenetic Tools to Counter TNF-α-Driven Inflammation.JACS Au · 2025Article
- Exploring the bioactive ingredients of three traditional Chinese medicine formulas against age-related hearing loss through network pharmacology and experimental validation.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumour necrosis factor (TNF) is a cytokine belonging to a family of trimeric proteins; it has been shown to be a key mediator in autoimmune diseases such as rheumatoid arthritis and Crohn's disease. While TNF is the target of several successful biologic drugs, attempts to design small molecule therapies directed to this cytokine have not led to approved products. Here we report the discovery of potent small molecule inhibitors of TNF that stabilise an asymmetrical form of the soluble TNF trimer, compromising signalling and inhibiting the functions of TNF in vitro and in vivo. This discovery paves the way for a class of small molecule drugs capable of modulating TNF function by stabilising a naturally sampled, receptor-incompetent conformation of TNF. Furthermore, this approach may prove to be a more general mechanism for inhibiting protein-protein interactions.
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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.