ArticleChemMedChem2014
Structure-based design of novel human Toll-like receptor 8 agonists.
Article in ChemMedChem, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 45 citations in OpenAlex.
- 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
- 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
- Transcriptomal signatures of vaccine adjuvants and accessory immunostimulation of sentinel cells by toll-like receptor 2/6 agonists.Human vaccines & immunotherapeutics · 2018Article
- Super Secondary Structure Consisting of a Polyproline II Helix and a β-Turn in Leucine Rich Repeats in Bacterial Type III Secretion System Effectors.The protein journal · 2018Article
- Selective evolution of Toll-like receptors 3, 7, 8, and 9 in bats.Immunogenetics · 2017Article
- GlycoMineScientific reports · 2016Article
- Virtual Screening Approaches towards the Discovery of Toll-Like Receptor Modulators.International journal of molecular sciences · 2016Review
- Strategies for designing synthetic immune agonists.Immunology · 2016Review
- Structural aspects of nucleic acid-sensing Toll-like receptors.Biophysical reviews · 2016Review
- Identification of Adjuvantic Activity of Amphotericin B in a Novel, Multiplexed, Poly-TLR/NLR High-Throughput Screen.PloS one · 2016Article
- Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity.Journal of medicinal chemistry · 2015Article
- Comparative Geometrical Analysis of Leucine-Rich Repeat Structures in the Nod-Like and Toll-Like Receptors in Vertebrate Innate Immunity.Biomolecules · 2015Review
- Toll-like receptor 8 senses degradation products of single-stranded RNA.Nature structural & molecular biology · 2015Article
- Determinants of activity at human Toll-like receptors 7 and 8: quantitative structure-activity relationship (QSAR) of diverse heterocyclic scaffolds.Journal of medicinal chemistry · 2014Article
- Human Toll-like receptor 8-selective agonistic activities in 1-alkyl-1H-benzimidazol-2-amines.Journal of medicinal chemistry · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Toll-like receptor (TLR)-8 agonists activate adaptive immune responses by inducing robust production of T helper 1-polarizing cytokines, suggesting that TLR8-active compounds might be promising candidate vaccine adjuvants. Recently, a C2-butyl furo[2,3-c]quinoline was reported with purely TLR8 agonistic activity. This compound was successfully co-crystallized with the human TLR8 ectodomain, and the co-crystal structure revealed ligand-induced reorganization of the binding pocket of TLR8. The loss of a key hydrogen bond between the oxygen atom of the furanyl ring of the agonist and Thr 574 in TLR8 suggested that the furan ring is dispensable. Employing a disconnection strategy, 3- and 4-substituted aminoquinolines were investigated. Focused structure-based ligand design studies led to the identification of 3-pentyl-quinoline-2-amine as a novel, structurally simple, and highly potent human TLR8-specific agonist (EC50 =0.2 μM). Preliminary evaluation of this compound in ex vivo human blood assay systems revealed that it retains prominent cytokine-inducing activity. Together, these results indicate the suitability of this compound as a novel vaccine adjuvant, warranting further investigation.
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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.