ArticleScientific reports2021
Development of a CNS-permeable reactivator for nerve agent exposure: an iterative, multi-disciplinary approach.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
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- Nanodiamond mediated delivery of pyridinium oxime antidotes to central nervous system for potential treatment of exposure to nerve agents.Chemico-biological interactions · 2025Article
- Mitigating organophosphate nerve agent, soman (GD), induced long-term neurotoxicity: Saracatinib, a Src Tyrosine Kinase inhibitor, as a potential countermeasure.Journal of neuroinflammation · 2025Article
- Accelerating countermeasure candidate discovery for A-series chemical warfare agent exposure.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Biphasic response of human iPSC-derived neural network activity following exposure to a sarin-surrogate nerve agent.Frontiers in cellular neuroscience · 2024Article
- Design of electron-donating group substituted 2-PAM analogs as antidotes for organophosphate insecticide poisoning.RSC advances · 2023Article
- Advances in Computational Approaches for Estimating Passive Permeability in Drug Discovery.Membranes · 2023Review
- Terrorism-Related Attacks in East Asia from 1970 through 2020.Prehospital and disaster medicine · 2023Observational
- Article
- Benzyl trichloroacetimidates as derivatizing agents for phosphonic acids related to nerve agents by EI-GC-MS during OPCW proficiency test scenarios.Scientific reports · 2022Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Nerve agents have experienced a resurgence in recent times with their use against civilian targets during the attacks in Syria (2012), the poisoning of Sergei and Yulia Skripal in the United Kingdom (2018) and Alexei Navalny in Russia (2020), strongly renewing the importance of antidote development against these lethal substances. The current standard treatment against their effects relies on the use of small molecule-based oximes that can efficiently restore acetylcholinesterase (AChE) activity. Despite their efficacy in reactivating AChE, the action of drugs like 2-pralidoxime (2-PAM) is primarily limited to the peripheral nervous system (PNS) and, thus, provides no significant protection to the central nervous system (CNS). This lack of action in the CNS stems from their ionic nature that, on one end makes them very powerful reactivators and on the other renders them ineffective at crossing the Blood Brain Barrier (BBB) to reach the CNS. In this report, we describe the use of an iterative approach composed of parallel chemical and in silico syntheses, computational modeling, and a battery of detailed in vitro and in vivo assays that resulted in the identification of a promising, novel CNS-permeable oxime reactivator. Additional experiments to determine acute and chronic toxicity are ongoing.
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