ArticleSLAS discovery : advancing life sciences R & D2017
An Innovative High-Throughput Screening Approach for Discovery of Small Molecules That Inhibit TNF Receptors.
Article in SLAS discovery : advancing life sciences R & D, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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.
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.
Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- Intra-cluster receptor density (IRD): A molecular switch for TNFR1 clusters' signaling.Science advances · 2026Article
- Discovery of Ligands for the TNFR1 Extracellular Domain Using Fragment-Based Drug Discovery.ChemMedChem · 2026Article
- Article
- TNF as a mediator of metabolic inflammation and body-brain interaction in obesity-driven neuroinflammation and neurodegeneration.Ageing research reviews · 2025Review
- Multiplexed Dark FRET Biosensors: An accessible live-cell platform for target- and cell-specific monitoring of protein-protein interactions in 2D and 3D model systems.Research square · 2025Article
- Targeting the inter-monomeric space of TNFR1 pre-ligand dimers: A novel binding pocket for allosteric modulators.Computational and structural biotechnology journal · 2025Article
- NfκBin: a machine learning based method for screening TNF-α induced NF-κB inhibitors.Frontiers in bioinformatics · 2025Article
- Application of Fluorescence- and Bioluminescence-Based Biosensors in Cancer Drug Discovery.Biosensors · 2024Review
- Peptide-based allosteric inhibitor targets TNFR1 conformationally active region and disables receptor-ligand signaling complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Nimesulide, a COX-2 inhibitor, sensitizes pancreatic cancer cells to TRAIL-induced apoptosis by promoting DR5 clustering †.Cancer biology & therapy · 2023Article
- Review
- TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.Nature reviews. Rheumatology · 2023Review
- Zafirlukast Is a Promising Scaffold for Selectively Inhibiting TNFR1 Signaling.ACS bio & med chem Au · 2023Article
- Discovery of a Non-competitive TNFR1 Antagonist Affibody with Picomolar Monovalent Potency That Does Not Affect TNFR2 Function.Molecular pharmaceutics · 2023Article
- Indirubin Inhibits TRAIL-Induced Activation of Death Receptor 5 in Jurkat Cells.Natural product communications · 2023Article
- Application of polymersomes in membrane protein study and drug discovery: Progress, strategies, and perspectives.Bioengineering & translational medicine · 2023Review
- A Large-Scale High-Throughput Screen for Modulators of SERCA Activity.Biomolecules · 2022Article
- Broad Tricyclic Ring Inhibitors Block SARS-CoV-2 Spike Function Required for Viral Entry.ACS infectious diseases · 2022Article
- The Screening of Therapeutic Peptides for Anti-Inflammation through Phage Display Technology.International journal of molecular sciences · 2022Review
- Immunosuppressant Therapies in COVID-19: Is the TNF Axis an Alternative?Pharmaceuticals (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor necrosis factor receptor 1 (TNFR1) is a transmembrane receptor that binds tumor necrosis factor or lymphotoxin-alpha and plays a critical role in regulating the inflammatory response. Upregulation of these ligands is associated with inflammatory and autoimmune diseases. Current treatments reduce symptoms by sequestering free ligands, but this can cause adverse side effects by unintentionally inhibiting ligand binding to off-target receptors. Hence, there is a need for new small molecules that specifically target the receptors, rather than the ligands. Here, we developed a TNFR1 FRET biosensor expressed in living cells to screen compounds from the NIH Clinical Collection. We used an innovative high-throughput fluorescence lifetime screening platform that has exquisite spatial and temporal resolution to identify two small-molecule compounds, zafirlukast and triclabendazole, that inhibit the TNFR1-induced IκBα degradation and NF-κB activation. Biochemical and computational docking methods were used to show that zafirlukast disrupts the interactions between TNFR1 pre-ligand assembly domain (PLAD), whereas triclabendazole acts allosterically. Importantly, neither compound inhibits ligand binding, proving for the first time that it is possible to inhibit receptor activation by targeting TNF receptor-receptor interactions. This strategy should be generally applicable to other members of the TNFR superfamily, as well as to oligomeric receptors in general.
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What OpenQuestion holds
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.