ArticleJournal of medicinal chemistry2015
Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Assessing the Risk of Myocarditis Post-COVID-19 Vaccination: A Systematic Review of Case Reports from 2023 to 2025.Cardiovascular toxicology · 2026Pooled it
- Chemical adaptation: bridging synthetic chemistry with drug development.Science China. Life sciences · 2026Review
- HBsAg and TLR7/8 dual-targeting antibody-drug conjugates induce sustained anti-HBV activity in AAV/HBV mice: a preliminary study.Antibody therapeutics · 2024Article
- Gap Junctions and Connexins in Microglia-Related Oxidative Stress and Neuroinflammation: Perspectives for Drug Discovery.Biomolecules · 2023Review
- Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants.Advanced drug delivery reviews · 2021Review
- Structural evolution of toll-like receptor 7/8 agonists from imidazoquinolines to imidazoles.RSC medicinal chemistry · 2021Review
- Tetrasubstituted imidazoles as incognito Toll-like receptor 8 a(nta)gonists.Nature communications · 2021Article
- Structural and functional understanding of the toll-like receptors.Protein science : a publication of the Protein Society · 2021Review
- BBIQ, a pure TLR7 agonist, is an effective influenza vaccine adjuvant.Human vaccines & immunotherapeutics · 2020Article
- Targeting the innate immune receptor TLR8 using small-molecule agents.Acta crystallographica. Section D, Structural biology · 2020Review
- Agonist and antagonist ligands of toll-like receptors 7 and 8: Ingenious tools for therapeutic purposes.European journal of medicinal chemistry · 2020Review
- Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations.Molecules (Basel, Switzerland) · 2019Article
- Discovery of New Selective Butyrylcholinesterase (BChE) Inhibitors with Anti-Aβ Aggregation Activity: Structure-Based Virtual Screening, Hit Optimization and Biological Evaluation.Molecules (Basel, Switzerland) · 2019Article
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- The emerging chemical patterns applied in predicting human toll-like receptor 8 agonists.MedChemComm · 2018Article
- Transcriptomal signatures of vaccine adjuvants and accessory immunostimulation of sentinel cells by toll-like receptor 2/6 agonists.Human vaccines & immunotherapeutics · 2018Article
- Antibacterial Evaluation and Virtual Screening of New Thiazolyl-Triazole Schiff Bases as Potential DNA-Gyrase Inhibitors.International journal of molecular sciences · 2018Article
- Small-molecule inhibition of TLR8 through stabilization of its resting state.Nature chemical biology · 2018Article
- Design and Synthesis of N1-Modified Imidazoquinoline Agonists for Selective Activation of Toll-like Receptors 7 and 8.ACS medicinal chemistry letters · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Human Toll-like receptor 8 (hTLR8) is expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. Engagement by TLR8 agonists evokes a distinct cytokine profile which favors the development of type 1 helper T cells. Crystal structures of the ectodomain of hTLR8 cocrystallized with two regioisomers of a dual TLR7/8-agonistic N1-substituted imidazoquinolines showed subtle differences in their interactions in the binding site of hTLR8. We hypothesized that the potency of a previously reported best-in-class pure TLR8 agonist, 3-pentylquinoline-2-amine, could be further enhanced by "designing in" functional groups that would mimic key intermolecular interactions that we had observed in the crystal structures. We performed a focused exploration of decorating the quinoline core with alkylamino groups at all possible positions. These studies have led to the identification of a novel TLR8 agonist that was ∼ 20-fold more potent than the parent compound and displays prominent adjuvantic activity in a rabbit model of immunization.
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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.