ArticleScientific reports2018
Small Molecule Analogues of the parasitic worm product ES-62 interact with the TIR domain of MyD88 to inhibit pro-inflammatory signalling.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- 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
- The allure of targets for novel drugs.RSC medicinal chemistry · 2024Review
- Reduction in creatine metabolites in macrophages exposed to small molecule analogues of the anti-inflammatory parasitic worm product ES-62.Parasite immunology · 2024Article
- Anti-Inflammatory Effects of Helminth-Derived Products: Potential Applications and Challenges in Diabetes Mellitus Management.Journal of inflammation research · 2024Review
- The biosynthesis and role of phosphorylcholine in pathogenic and nonpathogenic bacteria.Trends in microbiology · 2023Review
- Protection against lung pathology during obesity-accelerated ageing in mice by the parasitic worm product ES-62.Frontiers in immunology · 2023Article
- The parasitic worm product ES-62 protects the osteoimmunology axis in a mouse model of obesity-accelerated ageing.Frontiers in immunology · 2022Article
- Suppression of inflammatory arthritis by the parasitic worm product ES-62 is associated with epigenetic changes in synovial fibroblasts.PLoS pathogens · 2021Article
- Mining nematode protein secretomes to explain lifestyle and host specificity.PLoS neglected tropical diseases · 2021Article
- MyD88 and beyond: a perspective on MyD88-targeted therapeutic approach for modulation of host immunity.Immunologic research · 2021Review
- Mining Helminths for Novel Therapeutics.Trends in molecular medicine · 2021Review
- An increase in p62/NBR1 levels in melioidosis patients of Sri Lanka exhibit a characteristic of potential host biomarker.Journal of medical microbiology · 2020Article
- The Two Faces of Nematode Infection: Virulence and Immunomodulatory Molecules From Nematode Parasites of Mammals, Insects and Plants.Frontiers in microbiology · 2020Review
- Worms: Pernicious parasites or allies against allergies?Parasite immunology · 2019Review
- Failure of the Anti-Inflammatory Parasitic Worm Product ES-62 to Provide Protection in Mouse Models of Type I Diabetes, Multiple Sclerosis, and Inflammatory Bowel Disease.Molecules (Basel, Switzerland) · 2018Article
- Development of a Novel Backbone Cyclic Peptide Inhibitor of the Innate Immune TLR/IL1R Signaling Protein MyD88.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
ES-62 is a protein secreted by the parasitic worm Acanthocheilonema viteae that is anti-inflammatory by virtue of covalently attached phosphorylcholine. Previously we have reported that drug-like Small Molecule Analogues (SMAs) of its phosphorylcholine moiety can mimic ES-62 in protecting against disease development in certain mouse models of autoimmune and allergic conditions, due to them causing partial degradation of the TLR/IL-1R adaptor MyD88. We have now taken a molecular modelling approach to investigating the mechanism underlying this effect and this predicts that the SMAs interact directly with the MyD88 TIR domain. Further support for this is provided by assay of LPS-induced MyD88/NF-κB-driven secreted alkaline phosphatase (SEAP) reporter activity in commercially-available stably transfected (TLR4-MD2-NF-κB-SEAP) HEK293 cells, as SMA12b-mediated inhibition of such SEAP activity is blocked by its pre-incubation with recombinant MyD88-TIR domain. Direct binding of SMA12b to the TIR domain is also shown to inhibit homo-dimerization of the adaptor, an event that can explain the observed degradation of the adaptor and inhibition of subsequent downstream signalling. Thus, these new data identify initial events by which drug-like ES-62 SMAs, which we also demonstrate are able to inhibit cytokine production by human cells, homeostatically maintain "safe" levels of MyD88 signalling.
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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.