ArticleACS chemical neuroscience2025
Histidine Focused Covalent Inhibitors Targeting Acetylcholinesterase: A Computational Pipeline for Multisite Therapeutic Discovery in Alzheimer's Disease.
Article in ACS chemical neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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.
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Who cites it
4 citing papers in PubMed.
- Recent Advances in Pyrazole-Based Cholinesterase Inhibitors: Medicinal Chemistry Perspectives from 2020 to 2025.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Halogen-dependent electronic regulation of reactivity and acetylcholinesterase recognition in halomethyl acetates: a predictive DFT-docking framework.Journal of computer-aided molecular design · 2026Article
- Design, synthesis, and multitarget evaluation of thiosemicarbazone-sulfonamide hybrids as potent cholinesterase and MAO-A inhibitors with neuroblastoma-associated cytotoxicity.Scientific reports · 2026Article
- Protein kinases as therapeutic targets in Alzheimer's disease: challenges, insights, and new frontiers.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease affects over 10% of individuals above the age of 65, yet current treatments offer only limited and temporary relief. Acetylcholinesterase, a key enzyme in neurotransmitter breakdown, also contributes to disease progression by promoting β-amyloid aggregation. While previous studies have focused on the catalytic serine, a key proton transfer residue, His447 remains unexplored as a potential covalent binding site. In this study, we aim to interrupt the activation of Ser203 by covalently modifying His447, thereby shutting down the entire catalytic process. Here, we reported a computational pipeline to identify epoxide-based small molecules that covalently engage His447 and modulate AChE activity. From a curated library of >7,000 epoxides, three ligands (L5, L6, L7) were selected via covalent docking, molecular dynamics simulations, and drug-likeness profiling. Microsecond-scale simulations revealed stable binding across multiple subsites, with L5 exhibiting the most consistent RMSD and compact
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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 Socratic graph.