ArticleToxicon : official journal of the International Society on Toxinology2010
Identification of small-molecule inhibitors of ricin and shiga toxin using a cell-based high-throughput screen.
Article in Toxicon : official journal of the International Society on Toxinology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Biophysical and Biochemical Assays for Screening Small Molecule Inhibitors Targeting Toxin-Ribosome Interactions.Toxins · 2026Review
- Article
- Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- A review for cell-based screening methods in drug discovery.Biophysics reports · 2021Article
- Synthesis and Structural Characterization of Ricin Inhibitors Targeting Ribosome Binding Using Fragment-Based Methods and Structure-Based Design.Journal of medicinal chemistry · 2021Article
- [Highly toxic type Ⅱ ribosome-inactivating proteins ricin and abrin and their detection methods: a review].Se pu = Chinese journal of chromatography · 2021Review
- Small Molecule Inhibitors Targeting the Interaction of Ricin Toxin A Subunit with Ribosomes.ACS infectious diseases · 2020Article
- Novel small molecule retrograde transport blocker confers post-exposure protection against ricin intoxication.Acta pharmaceutica Sinica. B · 2020Article
- A Proof-of-Concept, Two-Tiered Approach for Ricin Detection Using Ambient Mass Spectrometry.RSC advances · 2020Article
- Functional Assays for Measuring the Catalytic Activity of Ribosome Inactivating Proteins.Toxins · 2018Review
- Review
- Toxicity of ricin A chain is reduced in mammalian cells by inhibiting its interaction with the ribosome.Toxicology and applied pharmacology · 2016Article
- Baicalin inhibits the lethality of ricin in mice by inducing protein oligomerization.The Journal of biological chemistry · 2015Article
- Antisecretory factor peptide AF-16 inhibits the secreted autotransporter toxin-stimulated transcellular and paracellular passages of fluid in cultured human enterocyte-like cells.Infection and immunity · 2015Article
- Article
- Selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Immunotoxins: the role of the toxin.Toxins · 2013Review
- A relatively low level of ribosome depurination by mutant forms of ricin toxin A chain can trigger protein synthesis inhibition, cell signaling and apoptosis in mammalian cells.The international journal of biochemistry & cell biology · 2012Article
- Optimized 5-membered heterocycle-linked pterins for the inhibition of Ricin Toxin A.ACS medicinal chemistry letters · 2012Article
- Real-time cytotoxicity assay for rapid and sensitive detection of ricin from complex matrices.PloS one · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The Category B agents, ricin and shiga toxin (Stx), are RNA N-glycosidases that target a highly conserved adenine residue within the sarcin-ricin loop of eukaryotic 28S ribosomal RNA. In an effort to identify small-molecule inhibitors of these toxins that could serve as lead compounds for potential therapeutics, we have developed a simple Vero cell-based high-throughput cytotoxicity assay and have used it to screen approximately 81,300 compounds in 17 commercially available chemical libraries. This initial screen identified approximately 300 compounds with weak (>or=30 to <50%), moderate (>or=50 to <80%), or strong (>or=80%) ricin inhibitory activity. Secondary analysis of 244 of these original "hits" was performed, and 20 compounds that were capable of reducing ricin cytotoxicity by >50% were chosen for further study. Four compounds demonstrated significant dose-dependent ricin inhibitory activity in the Vero cell-based assay, with 50% effective inhibitory concentration (EC(50)) values ranging from 25 to 60microM. The same 20 compounds were tested in parallel for the ability to inhibit ricin's and Stx1's enzymatic activities in an in vitro translation reaction. Three of the 20 compounds, including the most effective compound in the cell-based assay, had discernible anti-toxin activity. One compound in particular, 4-fluorophenyl methyl 2-(furan-2-yl)quinoline-4-carboxylate ("compound 8"), had 50% inhibitory concentration (IC(50)) of 30microM, a value indicating >10-fold higher potency than is the case for previously described ricin-Stx1 inhibitors. Computer modeling predicted that compound 8 is capable of docking within the ricin active site. In conclusion, we have used a simple high-throughput cell-based method to identify several new small-molecule inhibitors of ricin and Stx.
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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.