ArticleEnvironmental health perspectives2021
Profiling the Tox21 Chemical Collection for Acetylcholinesterase Inhibition.
Article in Environmental health perspectives, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Testing Strategies for Metabolite-Mediated Neurotoxicity.International journal of molecular sciences · 2025Review
- Application of cytochrome P450 enzyme assays to predict p53 inducers and AChE inhibitors that require metabolic activation.Toxicology and applied pharmacology · 2025Article
- Profiling the Tox21 Compound Library for Their Inhibitory Effects on Cytochrome P450 Enzymes.International journal of molecular sciences · 2025Article
- High-Throughput Screening to Advance In Vitro Toxicology: Accomplishments, Challenges, and Future Directions.Annual review of pharmacology and toxicology · 2024Review
- Definition of the Neurotoxicity-Associated Metabolic Signature Triggered by Berberine and Other Respiratory Chain Inhibitors.Antioxidants (Basel, Switzerland) · 2023Article
- In vitro profiling of pesticides within the Tox21 10K compound library for bioactivity and potential toxicity.Toxicology and applied pharmacology · 2023Article
- Identification of Potent and Selective Acetylcholinesterase/Butyrylcholinesterase Inhibitors by Virtual Screening.Journal of chemical information and modeling · 2023Article
- Validation of Acetylcholinesterase Inhibition Machine Learning Models for Multiple Species.Chemical research in toxicology · 2023Article
- Prediction of drug-induced liver injury and cardiotoxicity using chemical structure and in vitro assay data.Toxicology and applied pharmacology · 2022Article
- Use of Tox21 Screening Data to Evaluate the COVID-19 Drug Candidates for Their Potential Toxic Effects and Related Pathways.Frontiers in pharmacology · 2022Review
- Acetylcholinesterase Inhibition Assays for High-Throughput Screening.Methods in molecular biology (Clifton, N.J.) · 2022Article
- High-throughput screening for identifying acetylcholinesterase inhibitors: Insights on novel inhibitors and the use of liver microsomes.SLAS discovery : advancing life sciences R & D · 2022Article
- Prediction Models for Agonists and Antagonists of Molecular Initiation Events for Toxicity Pathways Using an Improved Deep-Learning-Based Quantitative Structure-Activity Relationship System.International journal of molecular sciences · 2021Article
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16 authors.
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Abstract
backgroundInhibition of acetylcholinesterase (AChE), a biomarker of organophosphorous and carbamate exposure in environmental and occupational human health, has been commonly used to identify potential safety liabilities. So far, many environmental chemicals, including drug candidates, food additives, and industrial chemicals, have not been thoroughly evaluated for their inhibitory effects on AChE activity. AChE inhibitors can have therapeutic applications (e.g., tacrine and donepezil) or neurotoxic consequences (e.g., insecticides and nerve agents).
objectivesThe objective of the current study was to identify environmental chemicals that inhibit AChE activity using
methodsTo identify AChE inhibitors rapidly and efficiently, we have screened the Toxicology in the 21st Century (Tox21) 10K compound library in a quantitative high-throughput screening (qHTS) platform by using the homogenous cell-based AChE inhibition assay and enzyme-based AChE inhibition assays (with or without microsomes). AChE inhibitors identified from the primary screening were further tested in monolayer or spheroid formed by SH-SY5Y and neural stem cell models. The inhibition and binding modes of these identified compounds were studied with time-dependent enzyme-based AChE inhibition assay and molecular docking, respectively.
resultsA group of known AChE inhibitors, such as donepezil, ambenonium dichloride, and tacrine hydrochloride, as well as many previously unreported AChE inhibitors, such as chelerythrine chloride and cilostazol, were identified in this study. Many of these compounds, such as pyrazophos, phosalone, and triazophos, needed metabolic activation. This study identified both reversible (e.g., donepezil and tacrine) and irreversible inhibitors (e.g., chlorpyrifos and bromophos-ethyl). Molecular docking analyses were performed to explain the relative inhibitory potency of selected compounds.
conclusionsOur tiered qHTS approach allowed us to generate a robust and reliable data set to evaluate large sets of environmental compounds for their AChE inhibitory activity. https://doi.org/10.1289/EHP6993.
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