ArticleNature chemical biology2018
Small-molecule inhibition of TLR8 through stabilization of its resting state.
Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 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.
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Who cites it
68 citing papers in PubMed, 138 citations in OpenAlex.
- Toll-Like Receptors in the Mechanism of Hexabromocyclododecane-Induced Production of Pro-Inflammatory Cytokines.Journal of applied toxicology : JAT · 2026Article
- The role of toll-like receptors in tributyltin-, dibutyltin-, and pentachlorophenol-induced stimulation of tumor necrosis factor-alpha (TNFα) production in human immune cells.Archives of toxicology · 2026Article
- Synthesis and Biological Activity of Azolo[Molecules (Basel, Switzerland) · 2026Review
- Heterodimerization with signaling-inert TLR8b converts TLR8a from proviral to antiviral sensor in Ctenopharyngodon idella.Cell communication and signaling : CCS · 2026Article
- The contributions of TLR2, TLR8 and TLR3 to direct and antibody-dependent enhancement of dengue virus serotype 2 infection.Npj viruses · 2026Article
- 2'-O-Methyl-guanosine RNA fragments antagonize TLR7 and TLR8 to limit autoimmunity.Nature immunology · 2026Article
- Clinical characteristics, management, and hematopoietic cell transplantation of patients with TLR8 gain-of-function.Blood advances · 2026Article
- Exploring potential biomarkers of NETosis-Related genes in spinal cord injury through machine learning and multi-omics analysis.Biochemistry and biophysics reports · 2026Article
- Genetically engineered senescence-resistant human mesenchymal progenitor cells promote spinal cord injury repair.Life medicine · 2026Article
- Revealing the Mechanism of Buzhong Yiqi Tang in Ameliorating Autoimmune ThyroiditisCombinatorial chemistry & high throughput screening · 2026Article
- Human neutrophils recognize group B streptococciFrontiers in immunology · 2026Article
- Discovery of Potent and Selective Quinoline-Based Toll-like Receptor 9 Antagonists.ACS medicinal chemistry letters · 2025Article
- Discovery of ETI41 and ETI60: novel selective endosomal Toll-like receptor inhibitors for the treatment of autoimmune diseases.Experimental & molecular medicine · 2025Article
- Agonists and Antagonists Show Different Unbinding Paths from the TLR8 Receptor.Journal of chemical information and modeling · 2025Article
- Toll-Like Receptors in Pentachlorophenol- and Dibutyltin-Induced Production of Pro-Inflammatory Cytokines, Interleukin (IL)-1β, and IL-6, by Human Immune Cells.Journal of applied toxicology : JAT · 2025Article
- Toll-like Receptor Gene Polymorphisms as Predictive Biomarkers for Response to Infliximab in Japanese Patients with Crohn's Disease.Diagnostics (Basel, Switzerland) · 2025Article
- Discovery of Novel Isoxazole-Based Small-Molecule Toll-Like Receptor 8 Antagonists.Journal of medicinal chemistry · 2025Article
- Correlation Studies Between Double-Stranded DNA and Diabetes Mellitus.Journal of diabetes research · 2025Article
- Extracellular microRNAs modulate human microglial function through TLR8.Frontiers in immunology · 2025Article
- Natural Compounds that Modulate Circadian Rhythms.Current topics in medicinal chemistry · 2025Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Endosomal Toll-like receptors (TLR3, TLR7, TLR8, and TLR9) are highly analogous sensors for various viral or bacterial RNA and DNA molecular patterns. Nonetheless, few small molecules can selectively modulate these TLRs. In this manuscript, we identified the first human TLR8-specific small-molecule antagonists via a novel inhibition mechanism. Crystal structures of two distinct TLR8-ligand complexes validated a unique binding site on the protein-protein interface of the TLR8 homodimer. Upon binding to this new site, the small-molecule ligands stabilize the preformed TLR8 dimer in its resting state, preventing activation. As a proof of concept of their therapeutic potential, we have demonstrated that these drug-like inhibitors are able to suppress TLR8-mediated proinflammatory signaling in various cell lines, human primary cells, and patient specimens. These results not only suggest a novel strategy for TLR inhibitor design, but also shed critical mechanistic insight into these clinically important immune receptors.
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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.