ArticleJournal of medicinal chemistry2014
Determinants of activity at human Toll-like receptors 7 and 8: quantitative structure-activity relationship (QSAR) of diverse heterocyclic scaffolds.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
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Who cites it
27 citing papers in PubMed, 71 citations in OpenAlex.
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- Lipid Trolling to Optimize AJournal of medicinal chemistry · 2024Article
- Design and Synthesis of Polyphenolic Imidazo[4,5-ACS pharmacology & translational science · 2024Article
- Identification of Maleimide-Fused Carbazoles as Novel Noncanonical Bone Morphogenetic Protein Synergizers.ACS pharmacology & translational science · 2023Article
- Comprehensive immunoprofiling and systematic adjuvant comparisons for identifying suitable vaccine: Adjuvant pairings.Human vaccines & immunotherapeutics · 2023Article
- Boron Trifluoride Etherate Promoted Regioselective 3-Acylation of Indoles with Anhydrides.Molecules (Basel, Switzerland) · 2022Article
- 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
- Structural and functional understanding of the toll-like receptors.Protein science : a publication of the Protein Society · 2021Review
- Inhibition of RNA-binding proteins with small molecules.Nature reviews. Chemistry · 2020Review
- 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
- Toll-Like Receptor 9 Agonists in Cancer.OncoTargets and therapy · 2020Review
- Development of Adamantane-Conjugated TLR7/8 Agonists for Supramolecular Delivery and Cancer Immunotherapy.Theranostics · 2019Article
- 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
- Article
- Cascade bicyclization of triethylammonium thiolates with hydrazines: efficient access to pyrazolo[3,4-c]quinolines.Organic & biomolecular chemistry · 2016Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Toll-like receptor (TLR) 7 and 8 agonists are potential vaccine adjuvants, since they directly activate APCs and enhance Th1-driven immune responses. Previous SAR investigations in several scaffolds of small molecule TLR7/8 activators pointed to the strict dependence of the selectivity for TLR7 vis-à-vis TLR8 on the electronic configurations of the heterocyclic systems, which we sought to examine quantitatively with the goal of developing "heuristics" to define structural requisites governing activity at TLR7 and/or TLR8. We undertook a scaffold-hopping approach, entailing the syntheses and biological evaluations of 13 different chemotypes. Crystal structures of TLR8 in complex with the two most active compounds confirmed important binding interactions playing a key role in ligand occupancy and biological activity. Density functional theory based quantum chemical calculations on these compounds followed by linear discriminant analyses permitted the classification of inactive, TLR8-active, and TLR7/8 dual-active compounds, confirming the critical role of partial charges in determining biological activity.
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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.