ArticleProceedings of the National Academy of Sciences of the United States of America2003
A low molecular weight mimic of the Toll/IL-1 receptor/resistance domain inhibits IL-1 receptor-mediated responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- Alcohol drinking sex-dependently regulates interleukin-1 pro-inflammatory signaling in the prefrontal cortex of mice and rhesus macaques.Brain, behavior, and immunity · 2026Article
- Ion Currents Mediated by TRPA1 Channels in Freshly Dissociated Rat Articular Chondrocytes: Biophysical Properties and Regulation by Inflammatory Processes.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Targeting Myeloid Differentiation Primary Response Protein 88 (MyD88) and Galectin-3 to Develop Broad-Spectrum Host-Mediated Therapeutics against SARS-CoV-2.International journal of molecular sciences · 2024Review
- Targeting MyD88: Therapeutic mechanisms and potential applications of the specific inhibitor ST2825.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Chronic ethanol induces a pro-inflammatory switch in interleukin-1β regulation of GABAergic signaling in the medial prefrontal cortex of male mice.Brain, behavior, and immunity · 2023Article
- Article
- MyD88: At the heart of inflammatory signaling and cardiovascular disease.Journal of molecular and cellular cardiology · 2021Review
- MyD88 and beyond: a perspective on MyD88-targeted therapeutic approach for modulation of host immunity.Immunologic research · 2021Review
- Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala.Brain sciences · 2019Article
- Mimicking Strategy for Protein-Protein Interaction Inhibitor Discovery by Virtual Screening.Molecules (Basel, Switzerland) · 2019Review
- The TIR/BB-loop mimetic AS-1 prevents Ang II-induced hypertensive cardiac hypertrophy via NF-κB dependent downregulation of miRNA-143.Scientific reports · 2019Article
- Development of a Novel Backbone Cyclic Peptide Inhibitor of the Innate Immune TLR/IL1R Signaling Protein MyD88.Scientific reports · 2018Article
- Small Molecule Mimetics of α-Helical Domain of IRAK2 Attenuate the Proinflammatory Effects of IL-33 in Asthma-like Mouse Models.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- The TIR/BB-loop mimetic AS-1 prevents non-alcoholic steatohepatitis and hepatic insulin resistance by inhibiting NLRP3-ASC inflammasome activation.British journal of pharmacology · 2017Article
- Cytokines and cytokine networks target neurons to modulate long-term potentiation.Cytokine & growth factor reviews · 2017Article
- The Role of Toll-Like Receptors in Autoimmune Diseases through Failure of the Self-Recognition Mechanism.International journal of inflammation · 2017Review
- Fluorofenidone attenuates pulmonary inflammation and fibrosis via inhibiting the activation of NALP3 inflammasome and IL-1β/IL-1R1/MyD88/NF-κB pathway.Journal of cellular and molecular medicine · 2016Article
- The critical role of toll-like receptors--From microbial recognition to autoimmunity: A comprehensive review.Autoimmunity reviews · 2016Review
- Toll-Like Receptors in the Pathogenesis of Autoimmune Diseases.Advanced pharmaceutical bulletin · 2015Review
- Synapse-specific IL-1 receptor subunit reconfiguration augments vulnerability to IL-1β in the aged hippocampus.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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Authors and funding
6 authors.
Funding
Abstract
Toll-like receptors (TLRs) and the type I IL-1 receptor (IL-1RI) are key components of the innate immune system activated by microbial infections and inflammation. The signaling cascade from agonist-occupied TLRs and IL-1Rs involves recruitment of the small cytosolic adapter protein MyD88 that binds to IL-1RI via homotypic interactions mediated by Toll/IL-1R/resistance (TIR) domains. Dominant negative forms and null mutations of MyD88 have recently been shown to preclude bacterial product or IL-1-mediated activation of NF-kappaB pathways, demonstrating that MyD88 is an essential component of the Toll receptor signaling. Here, we report the synthesis and pharmacological effects of a low molecular weight MyD88 mimic, hydrocinnamoyl-l-valyl pyrrolidine (compound 4a), modeled on a tripeptide sequence of the BB-loop [(F/Y)-(V/L/I)-(P/G)] of the TIR domain. Results are presented showing that compound 4a interferes with the interactions between mouse MyD88 and IL-1RI at the TIR domains. Compound 4a inhibited IL-1beta-induced phosphorylation of the mitogen-activated protein kinase p38 in EL4 thymoma cells and in freshly isolated murine lymphocytes in a concentration-dependent manner. In vivo, compound 4a produced a significant attenuation of the IL-1beta-induced fever response (200 mg/kg, i.p.). Inhibition of the TIR domain-mediated MyD88/IL1-RI interaction by a low molecular weight, cell-penetrating TIR domain mimic suggests an intracellular site for antiinflammatory drug action.
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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.