ArticleScientific reports2015
Discovery of small molecule inhibitors of MyD88-dependent signaling pathways using a computational screen.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Role of Adaptor Protein Myeloid Differentiation 88 (MyD88) in Post-Subarachnoid Hemorrhage Inflammation: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Dysregulation of the TLR4/MYD88 Signaling Pathway in Egyptian Females with Breast Cancer: Implications for Tumor Progression.Molecular biology reports · 2026Article
- Review
- MyD88 self-assembles into supramolecular filaments to amplify NF-κB signaling.Fundamental research · 2026Article
- Enhanced Epigenetic Modulation via mRNA-Encapsulated Lipid Nanoparticles Enables Targeted Anti-inflammatory Control.ACS synthetic biology · 2026Article
- In silico analysis of Triphala-derived polyphenols as inhibitors of TIR-TIR homodimerization in the inflammatory pathway.Frontiers in bioinformatics · 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
- MyD88 and Its Inhibitors in Cancer: Prospects and Challenges.Biomolecules · 2024Review
- A mosquito salivary protein-driven influx of myeloid cells facilitates flavivirus transmission.The EMBO journal · 2024Article
- The allure of targets for novel drugs.RSC medicinal chemistry · 2024Review
- MyD88 signaling pathways: role in breast cancer.Frontiers in oncology · 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
- Article
- The oncogenic human B-cell lymphoma MYD88 L265P mutation genocopies activation by phosphorylation at the Toll/interleukin-1 receptor (TIR) domain.Blood cancer journal · 2023Article
- Article
- Osteocytes directly regulate osteolysis via MYD88 signaling in bacterial bone infection.Nature communications · 2022Article
- Review
- Structure-based virtual screening workflow to identify antivirals targeting HIV-1 capsid.Journal of computer-aided molecular design · 2022Article
- Lipopolysaccharide sensitizes the therapeutic response of breast cancer to IAP antagonist.Frontiers in immunology · 2022Article
- The role of B cells in the development, progression, and treatment of lymphomas and solid tumors.Advances in immunology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
In this study, we used high-throughput computational screening to discover drug-like inhibitors of the host MyD88 protein-protein signaling interaction implicated in the potentially lethal immune response associated with Staphylococcal enterotoxins. We built a protein-protein dimeric docking model of the Toll-interleukin receptor (TIR)-domain of MyD88 and identified a binding site for docking small molecules. Computational screening of 5 million drug-like compounds led to testing of 30 small molecules; one of these molecules inhibits the TIR-TIR domain interaction and attenuates pro-inflammatory cytokine production in human primary cell cultures. Compounds chemically similar to this hit from the PubChem database were observed to be more potent with improved drug-like properties. Most of these 2(nd) generation compounds inhibit Staphylococcal enterotoxin B (SEB)-induced TNF-α, IFN-γ, IL-6, and IL-1β production at 2-10 μM in human primary cells. Biochemical analysis and a cell-based reporter assay revealed that the most promising compound, T6167923, disrupts MyD88 homodimeric formation, which is critical for its signaling function. Furthermore, we observed that administration of a single dose of T6167923 completely protects mice from lethal SEB-induced toxic shock. In summary, our in silico approach has identified anti-inflammatory inhibitors against in vitro and in vivo toxin exposure with promise to treat other MyD88-related pro-inflammatory diseases.
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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.