ArticleThe Journal of biological chemistry2020
Rational design, synthesis, and evaluation of uncharged, "smart" bis-oxime antidotes of organophosphate-inhibited human acetylcholinesterase.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
18 citing papers in PubMed, 42 citations in OpenAlex.
- Next-generation broad-spectrum reactivators for effective countermeasure against organophosphorus poisoning.Archives of toxicology · 2026Article
- From Mechanisms to Materials: Oximate Reactivity and Emerging Strategies for Organophosphate Detoxification.Chemphyschem : a European journal of chemical physics and physical chemistry · 2026Review
- Imidazole as a Pendant Reactivation Ligand Increases Efficacy Scope for Reactivation and Resurrection of Organophosphorus-Inhibited/Aged Cholinesterases by Quinone Methide Precursors.ACS chemical neuroscience · 2026Article
- Nanodiamond mediated delivery of pyridinium oxime antidotes to central nervous system for potential treatment of exposure to nerve agents.Chemico-biological interactions · 2025Article
- Kinetic and structural evidence for specific DMSO interference with reversible binding of uncharged bis-oximes to hAChE and their reactivation kinetics of OP-hAChE.Chemico-biological interactions · 2025Article
- Acetylcholinesterase: Structure, dynamics, and interactions with organophosphorus compounds.Protein science : a publication of the Protein Society · 2025Review
- Molecular docking and molecular dynamics simulations revealed interaction mechanism of acetylcholinesterase with organophosphorus pesticides and their alternatives.Archives of toxicology · 2025Article
- Application of in silico methods to predict the acute toxicity of bicyclic organophosphorus compounds as potential chemical weapon.Archives of toxicology · 2025Article
- Identification ofMolecules (Basel, Switzerland) · 2025Article
- Cholesterol Oxime Olesoxime Assessed as a Potential Ligand of Human Cholinesterases.Biomolecules · 2024Article
- Structural and dynamic effects of paraoxon binding to human acetylcholinesterase by X-ray crystallography and inelastic neutron scattering.Structure (London, England : 1993) · 2022Article
- Pyrazoline Containing Compounds as Therapeutic Targets for Neurodegenerative Disorders.ACS omega · 2022Review
- FDA-Approved Oximes and Their Significance in Medicinal Chemistry.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Assessment of four organophosphorus pesticides as inhibitors of human acetylcholinesterase and butyrylcholinesterase.Scientific reports · 2021Article
- Dual acting oximes designed for therapeutic decontamination of reactive organophosphatesRSC medicinal chemistry · 2021Article
- Development of a CNS-permeable reactivator for nerve agent exposure: an iterative, multi-disciplinary approach.Scientific reports · 2021Article
- A Thermophilic Bacterial Esterase for Scavenging Nerve Agents: A Kinetic, Biophysical and Structural Study.Molecules (Basel, Switzerland) · 2021Article
- Room temperature crystallography of human acetylcholinesterase bound to a substrate analogue 4K-TMA: Towards a neutron structure.Current research in structural biology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Organophosphate (OP) intoxications from nerve agent and OP pesticide exposures are managed with pyridinium aldoxime-based therapies whose success rates are currently limited. The pyridinium cation hampers uptake of OPs into the central nervous system (CNS). Furthermore, it frequently binds to aromatic residues of OP-inhibited acetylcholinesterase (AChE) in orientations that are nonproductive for AChE reactivation, and the structural diversity of OPs impedes efficient reactivation. Improvements of OP antidotes need to include much better access of AChE reactivators to the CNS and optimized orientation of the antidotes' nucleophile within the AChE active-center gorge. On the basis of X-ray structures of a CNS-penetrating reactivator, monoxime RS194B, reversibly bound to native and venomous agent X (VX)-inhibited human AChE, here we created seven uncharged acetamido bis-oximes as candidate antidotes. Both oxime groups in these bis-oximes were attached to the same central, saturated heterocyclic core. Diverse protonation of the heterocyclic amines and oxime groups of the bis-oximes resulted in equilibration among up to 16 distinct ionization forms, including uncharged forms capable of diffusing into the CNS and multiple zwitterionic forms optimal for reactivation reactions. Conformationally diverse zwitterions that could act as structural antidote variants significantly improved
Indexed as
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.