ArticleScience signaling2012
Selective TRIF-dependent signaling by a synthetic toll-like receptor 4 agonist.
Article in Science signaling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 77 citations in OpenAlex.
- Synthesis of Acinetobacter baumannii Lipid A(s) and derivatives and their structure-immunostimulatory activity relationships.Communications chemistry · 2025Article
- Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling.Nature communications · 2024Article
- RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling.Nature communications · 2024Article
- Surface immunogenic protein from Streptococcus agalactiae andFrontiers in immunology · 2023Article
- Review: Current trends, challenges, and success stories in adjuvant research.Frontiers in immunology · 2023Review
- CRX-527 induced differentiation of HSCs protecting the intestinal epithelium from radiation damage.Frontiers in immunology · 2022Article
- Dissociation of TRIF bias and adjuvanticity.Vaccine · 2020Article
- TLR4-Targeting Therapeutics: Structural Basis and Computer-Aided Drug Discovery Approaches.Molecules (Basel, Switzerland) · 2020Review
- Immunobiology and application of toll-like receptor 4 agonists to augment host resistance to infection.Pharmacological research · 2019Review
- Funiculosin variants and phosphorylated derivatives promote innate immune responses via the Toll-like receptor 4/myeloid differentiation factor-2 complex.The Journal of biological chemistry · 2017Article
- Old and new adjuvants.Current opinion in immunology · 2017Review
- Article
- A structure-function approach to optimizing TLR4 ligands for human vaccines.Clinical & translational immunology · 2016Article
- HIV-1 Tat Protein Activates both the MyD88 and TRIF Pathways To Induce Tumor Necrosis Factor Alpha and Interleukin-10 in Human Monocytes.Journal of virology · 2016Article
- Pharmacological characterization of the opioid inactive isomers (+)-naltrexone and (+)-naloxone as antagonists of toll-like receptor 4.British journal of pharmacology · 2016Article
- Identification of Adjuvantic Activity of Amphotericin B in a Novel, Multiplexed, Poly-TLR/NLR High-Throughput Screen.PloS one · 2016Article
- Differential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Synthesis ofTetrahedron letters · 2015Article
- Kdo2 -lipid A: structural diversity and impact on immunopharmacology.Biological reviews of the Cambridge Philosophical Society · 2015Review
- Characterization of TRIF selectivity in the AGP class of lipid A mimetics: role of secondary lipid chains.Bioorganic & medicinal chemistry letters · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
In response to ligand binding to the Toll-like receptor 4 (TLR4) and myeloid differentiation-2 (MD-2) receptor complex, two major signaling pathways are activated that involve different adaptor proteins. One pathway depends on myeloid differentiation marker 88 (MyD88), which elicits proinflammatory responses, whereas the other depends on Toll-IL-1 receptor (TIR) domain-containing adaptor inducing interferon-β (TRIF), which elicits type I interferon production. Here, we showed that the TLR4 agonist and vaccine adjuvant CRX-547, a member of the aminoalkyl glucosaminide 4-phosphate (AGP) class of synthetic lipid A mimetics, displayed TRIF-selective signaling in human cells, which was dependent on a minor structural modification to the carboxyl bioisostere corresponding to the 1-phosphate group on most lipid A types. CRX-547 stimulated little or no activation of MyD88-dependent signaling molecules or cytokines, whereas its ability to activate the TRIF-dependent pathway was similar to that of a structurally related inflammatory AGP and of lipopolysaccharide from Salmonella minnesota. This TRIF-selective signaling response resulted in the production of substantially less of the proinflammatory mediators that are associated with MyD88 signaling, thereby potentially reducing toxicity and improving the therapeutic index of this synthetic TLR4 agonist and vaccine adjuvant.
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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.