ArticleToxins2010
Identification of Small Molecule Inhibitors of Clostridium perfringens ε-Toxin Cytotoxicity Using a Cell-Based High-Throughput Screen.
Article in Toxins, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Story of Pore-Forming Proteins from Deadly Disease-Causing Agents to Modern Applications with Evolutionary Significance.Molecular biotechnology · 2024Review
- Article
- Statins as Potential Preventative Treatment of ETX and Multiple Pore-Forming Toxin-Induced Diseases.International journal of molecular sciences · 2023Article
- Lung endothelial cells are sensitive to epsilon toxin from Clostridium perfringens.Veterinary research · 2020Article
- A small bioactive glycoside inhibits epsilon toxin and prevents cell death.Disease models & mechanisms · 2019Article
- Inhibition of bacterial toxin recognition of membrane components as an anti-virulence strategy.Journal of biological engineering · 2019Review
- Pharmacological Targeting of Pore-Forming Toxins as Adjunctive Therapy for Invasive Bacterial Infection.Toxins · 2018Review
- Inhibition of Clostridium perfringens epsilon toxin by β-cyclodextrin derivatives.International journal of pharmaceutics · 2017Article
- Inhibiting bacterial toxins by channel blockage.Pathogens and disease · 2016Review
- The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of Clostridium perfringens ε-Toxin.PLoS pathogens · 2015Article
- Review
- Identification of novel compounds inhibiting chikungunya virus-induced cell death by high throughput screening of a kinase inhibitor library.PLoS neglected tropical diseases · 2013Article
- Obstructing toxin pathways by targeted pore blockage.Chemical reviews · 2012Review
- Identification of amino acids important for binding of Clostridium perfringens epsilon toxin to host cells and to HAVCR1.Biochemistry · 2012Article
- Coenzyme depletion by members of the aerolysin family of pore-forming toxins leads to diminished ATP levels and cell death.Molecular bioSystems · 2012Article
- Oligomerization of Clostridium perfringens epsilon toxin is dependent upon caveolins 1 and 2.PloS one · 2012Article
- Gene-trap mutagenesis identifies mammalian genes contributing to intoxication by Clostridium perfringens ε-toxin.PloS one · 2011Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The Clostridium perfringens epsilon toxin, a select agent, is responsible for a severe, often fatal enterotoxemia characterized by edema in the heart, lungs, kidney, and brain. The toxin is believed to be an oligomeric pore-forming toxin. Currently, there is no effective therapy for countering the cytotoxic activity of the toxin in exposed individuals. Using a robust cell-based high-throughput screening (HTS) assay, we screened a 151,616-compound library for the ability to inhibit ε-toxin-induced cytotoxicity. Survival of MDCK cells exposed to the toxin was assessed by addition of resazurin to detect metabolic activity in surviving cells. The hit rate for this screen was 0.6%. Following a secondary screen of each hit in triplicate and assays to eliminate false positives, we focused on three structurally-distinct compounds: an N-cycloalkylbenzamide, a furo[2,3-b]quinoline, and a 6H-anthra[1,9-cd]isoxazol. None of the three compounds appeared to inhibit toxin binding to cells or the ability of the toxin to form oligomeric complexes. Additional assays demonstrated that two of the inhibitory compounds inhibited ε-toxin-induced permeabilization of MDCK cells to propidium iodide. Furthermore, the two compounds exhibited inhibitory effects on cells pre-treated with toxin. Structural analogs of one of the inhibitors identified through the high-throughput screen were analyzed and provided initial structure-activity data. These compounds should serve as the basis for further structure-activity refinement that may lead to the development of effective anti-ε-toxin therapeutics.
Identifiers
What OpenQuestion holds
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.