ArticleThe Journal of biological chemistry2010
Identification of novel synthetic toll-like receptor 2 agonists by high throughput screening.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 63 citations in OpenAlex.
- Discovery of Novel Small-Molecule Toll-like Receptor 2 Agonists via a Scaffold Hopping Strategy.ACS medicinal chemistry letters · 2026Article
- Identification of CDK4/6 Inhibitors as Small Molecule NLRP3 Inflammasome Activators that Facilitate IL-1β Secretion and T Cell Adjuvanticity.Journal of medicinal chemistry · 2024Article
- Therapeutic synthetic and natural materials for immunoengineering.Chemical Society reviews · 2024Review
- Article
- Small molecule modulators of immune pattern recognition receptors.RSC chemical biology · 2023Review
- Recent Advances in Studying Toll-like Receptors with the Use of Computational Methods.Journal of chemical information and modeling · 2023Review
- Precision Vaccinology Approaches for the Development of Adjuvanted Vaccines Targeted to Distinct Vulnerable Populations.Pharmaceutics · 2023Review
- Discovery of New States of Immunomodulation for Vaccine Adjuvants via High Throughput Screening: Expanding Innate Responses to PRRs.ACS central science · 2023Article
- Next-Generation Diprovocims with Potent Human and Murine TLR1/TLR2 Agonist Activity That Activate the Innate and Adaptive Immune Response.Journal of medicinal chemistry · 2022Article
- Small Molecule Calcium Channel Activator Potentiates Adjuvant Activity.ACS chemical biology · 2022Article
- Emerging concepts in the science of vaccine adjuvants.Nature reviews. Drug discovery · 2021Review
- Biological Characterization, Mechanistic Investigation and Structure-Activity Relationships of Chemically Stable TLR2 Antagonists.ChemMedChem · 2020Article
- Nanomedicine-mediated alteration of the pharmacokinetic profile of small molecule cancer immunotherapeutics.Acta pharmacologica Sinica · 2020Review
- Emerging Adjuvants for Cancer Immunotherapy.Frontiers in chemistry · 2020Review
- Selection of adjuvants for vaccines targeting specific pathogens.Expert review of vaccines · 2019Review
- Structural Basis of TLR2/TLR1 Activation by the Synthetic Agonist Diprovocim.Journal of medicinal chemistry · 2019Article
- Immunomodulatory nanogels overcome restricted immunity in a murine model of gut microbiome-mediated metabolic syndrome.Science advances · 2019Article
- Targeting Cellular and Tissue HIV Reservoirs With Toll-Like Receptor Agonists.Frontiers in immunology · 2019Review
- Diprovocims: A New and Exceptionally Potent Class of Toll-like Receptor Agonists.Journal of the American Chemical Society · 2018Article
- Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in mice.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Toll-like receptors (TLRs) play a central role in host defense by inducing inflammatory and adaptive immune responses following infection. Drugs that target TLRs are of considerable interest as potential inflammatory regulators, vaccine adjuvants, and novel immunotherapeutics. TLR2, in cooperation with either TLR1 or TLR6, mediates responses to a wide variety of microbial products as well as products of host tissue damage. In an effort to understand the structural basis of TLR2 recognition and uncover novel TLR2 agonists, a synthetic chemical library of 24,000 compounds was screened using an IL-8-driven luciferase reporter in cells expressing these human receptors. The screening yielded several novel TLR2-dependent activators that utilize TLR1, TLR6, or both as co-receptors. These novel small molecule compounds are aromatic in nature and structurally unrelated to any known TLR2 agonists. The three most potent compounds do not exhibit synergistic activity, nor do they act as pseudoantagonists toward natural TLR2 activators. Interestingly, two of the compounds exhibit species specificity and are inactive toward murine peritoneal macrophages. Mutational analysis reveals that although the central extracellular region of TLR1 is required for stimulation, there are subtle differences in the mechanism of stimulation mediated by the synthetic compounds in comparison with natural lipoprotein agonists. The three most potent compounds activate cells in the nanomolar range and stimulate cytokine production from human peripheral blood monocytes. Our results confirm the utility of high throughput screens to uncover novel synthetic TLR2 agonists that may be of therapeutic benefit.
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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.