ArticleJournal of medicinal chemistry2019
Structural Basis of TLR2/TLR1 Activation by the Synthetic Agonist Diprovocim.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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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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
45 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- The immunoproteome and multimorbidity: A Mendelian randomization study.Science advances · 2026Article
- LGALS3BP Induces Insulin Resistance via TLR2-IKKα/β Pathway-Mediated IRS1 Serine Phosphorylation.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- Targeting SOX9: designing a novel vaccine against triple-negative breast cancer.Scientific reports · 2025Article
- Factors Driving Amyloid Beta Fibril Recognition by Cell Surface Receptors: A Computational Study.Molecules (Basel, Switzerland) · 2025Article
- Pattern recognition receptors: function, regulation and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- TLR2 and TLR4 bridge physiological and pathological inflammation in the reproductive system.Communications biology · 2025Review
- Immunotoxicity Study of Cucurbit[n]urils (n = 6, 7, 8) and Modeling of Interaction with Some Monocyte Receptors by a Molecular Docking Method.Molecules (Basel, Switzerland) · 2025Article
- Diprovocim protects against the radiation-induced damage via the TLR2 signaling pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- The intracellular domain of TLR2 is capable of high-affinity Zn binding: possible outcomes for the receptor activation.FEBS letters · 2025Article
- Dampened TLR2-mediated Inflammatory Signaling in Bats.Molecular biology and evolution · 2025Article
- Article
- A multi-epitope vaccine incorporating adhesin-derived antigens protects againstFrontiers in immunology · 2025Article
- The Possible Mechanistic Basis of Individual Susceptibility to Spike Protein Injury.Advances in virology · 2025Review
- Article
- Multi-epitope peptide vaccines targeting dengue virus serotype 2 created via immunoinformatic analysis.Scientific reports · 2024Article
- Immunomodulatory Peptides as Vaccine Adjuvants and Antimicrobial Agents.Pharmaceuticals (Basel, Switzerland) · 2024Article
- TIR domains of TLR family-from the cell culture to the protein sample for structural studies.PloS one · 2024Article
- Anticipatory in silico vaccine designing based on specific antigenic epitopes fromIn silico pharmacology · 2024Article
- Small molecule modulators of immune pattern recognition receptors.RSC chemical biology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Diprovocim is a recently discovered exceptionally potent, synthetic small molecule agonist of TLR2/TLR1 and has shown significant adjuvant activity in anticancer vaccination against murine melanoma. Since Diprovocim bears no structural similarity to the canonical lipopeptide ligands of TLR2/TLR1, we investigated how Diprovocim interacts with TLR2/TLR1 through in vitro biophysical, structural, and computational approaches. We found that Diprovocim induced the formation of TLR2/TLR1 heterodimers as well as TLR2 homodimers in vitro. We determined the crystal structure of Diprovocim in a complex with a TLR2 ectodomain, which revealed, unexpectedly, two Diprovocim molecules bound to the ligand binding pocket formed between two TLR2 ectodomains. Extensive hydrophobic interactions and a hydrogen-bonding network between the protein and Diprovocim molecules are observed within the defined ligand binding pocket and likely underlie the high potency of Diprovocim. Our work shed first light into the activation mechanism of TLR2/TLR1 by a noncanonical agonist. The structural information obtained here may be exploited to manipulate TLR2/TLR1-dependent signaling.
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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 Socratic graph.