ArticleProceedings of the National Academy of Sciences of the United States of America2013
Selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 91 citations in OpenAlex.
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- Endosomal trafficking inhibitor EGA can control TLR7-mediated IFNα expression by human plasmacytoid dendritic cells.Frontiers in immunology · 2023Article
- Disruption of endosomal trafficking with EGA alters TLR9 cytokine response in human plasmacytoid dendritic cells.Frontiers in immunology · 2023Article
- LAMP3/CD63 Expression in Early and Late Endosomes in Human Vaginal Epithelial Cells Is Associated with Enhancement of HSV-2 Infection.Journal of virology · 2022Article
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- C910 chemical compound inhibits the traffiking of several bacterial AB toxins with cross-protection against influenza virus.iScience · 2022Article
- Exotoxin-Targeted Drug Modalities as Antibiotic Alternatives.ACS infectious diseases · 2022Review
- Optogenetic Control of Membrane Trafficking Using Light-Activated Reversible Inhibition by Assembly Trap of Intracellular Membranes (IM-LARIAT).Methods in molecular biology (Clifton, N.J.) · 2022Article
- Broad-spectrum Respiratory Virus Entry Inhibitors.Advances in experimental medicine and biology · 2022Article
- Loss of E-Cadherin Leads to Druggable Vulnerabilities in Sphingolipid Metabolism and Vesicle Trafficking.Cancers · 2021Article
- Novel Small Molecule Inhibitors That Prevent the Neuroparalysis of Tetanus Neurotoxin.Pharmaceuticals (Basel, Switzerland) · 2021Article
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20 authors at 5 institutions in 1 country.
Funding
Abstract
Pathogenic microorganisms and toxins have evolved a variety of mechanisms to gain access to the host-cell cytosol and thereby exert virulent effects upon the host. One common mechanism of cellular entry requires trafficking to an acidified endosome, which promotes translocation across the host membrane. To identify small-molecule inhibitors that block this process, a library of 30,000 small molecules was screened for inhibitors of anthrax lethal toxin. Here we report that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone, the most active compound identified in the screen, inhibits intoxication by lethal toxin and blocks the entry of multiple other acid-dependent bacterial toxins and viruses into mammalian cells. This compound, which we named EGA, also delays lysosomal targeting and degradation of the EGF receptor, indicating that it targets host-membrane trafficking. In contrast, EGA does not block endosomal recycling of transferrin, retrograde trafficking of ricin, phagolysosomal trafficking, or phagosome permeabilization by Franciscella tularensis. Furthermore, EGA does not neutralize acidic organelles, demonstrating that its mechanism of action is distinct from pH-raising agents such as ammonium chloride and bafilomycin A1. EGA is a powerful tool for the study of membrane trafficking and represents a class of host-targeted compounds for therapeutic development to treat infectious disease.
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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.