Accelerating countermeasure candidate discovery for A-series chemical warfare agent exposure

Morato, Nicolás M.; Mason, Katelyn E.; Corzett, Todd H.; Valdez, Carlos A.; Alfaro, Teneile M.; Hok, Saphon; Cooks, R. Graham; Mayer, Brian P.

doi:10.1073/pnas.2512471122

Title: Accelerating countermeasure candidate discovery for A-series chemical warfare agent exposure

Journal Article · Thu Jul 17 00:00:00 UTC 2025 · Proceedings of the National Academy of Sciences of the United States of America

DOI: https://doi.org/10.1073/pnas.2512471122 · OSTI ID:2585271

Morato, Nicolás M. ^[1];

^[2];

^[1];

^[2]

Purdue Univ., West Lafayette, IN (United States)
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

The recent alleged use of A-series chemical warfare agents (CWAs) highlights the urgent need to better understand their inhibition of cholinesterase enzymes and the reported shortcomings of traditional oxime countermeasures. Here, using high-throughput (HT) mass spectrometry (MS) technologies, we characterized the largely unknown inhibition kinetics of A-series CWAs on human acetylcholinesterase (hAChE) and its reactivation by oximes, achieving label-free quantitation at rates of up to 7,000 reactions per hour. Our findings indicate i) A-series agents exhibit inhibitory potencies similar to traditional CWAs like sarin and VX, and ii) bipyridinium-based oximes can reactivate A-series-adducted hAChE in vitro, challenging prior reports on oxime efficacy. These results underscore the need for continued exploration of countermeasure candidates against A-series CWAs and demonstrate the potential of HT-MS for rapidly and safely characterizing emerging toxic chemicals.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 2585271

Report Number(s):: LLNL--JRNL-2002371

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 29 Vol. 122; ISSN 1091-6490; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

References (76)

Mass Activated Droplet Sorting (MADS) Enables High‐Throughput Screening of Enzymatic Reactions at Nanoliter Scale Holland‐Moritz, Daniel A.; Wismer, Michael K.; Mann, Benjamin F. Angewandte Chemie International Edition, Vol. 59, Issue 11 https://doi.org/10.1002/anie.201913203	journal	January 2020
High‐Throughput Label‐Free Enzymatic Assays Using Desorption Electrospray‐Ionization Mass Spectrometry Morato, Nicolás M.; Holden, Dylan T.; Cooks, R. Graham Angewandte Chemie International Edition, Vol. 59, Issue 46 https://doi.org/10.1002/anie.202009598	journal	September 2020
High‐Throughput Diversification of Complex Bioactive Molecules by Accelerated Synthesis in Microdroplets Huang, Kai‐Hung; Morato, Nicolás M.; Feng, Yunfei Angewandte Chemie International Edition, Vol. 62, Issue 22 https://doi.org/10.1002/anie.202300956	journal	April 2023
Desorption Electrospray Ionization Mass Spectrometry Assay for Label‐Free Characterization of SULT2B1b Enzyme Kinetics Kulathunga, Samadhi C.; Morato, Nicolás M.; Zhou, Qing ChemMedChem, Vol. 17, Issue 9 https://doi.org/10.1002/cmdc.202200043	journal	February 2022
A Comprehensive Guide for Assessing Covalent Inhibition in Enzymatic Assays Illustrated with Kinetic Simulations Mons, Elma; Roet, Sander; Kim, Robbert Q. Current Protocols, Vol. 2, Issue 6 https://doi.org/10.1002/cpz1.419	journal	June 2022
Re‐Imagining Drug Discovery using Mass Spectrometry Cooks, R. Graham; Feng, Yunfei; Huang, Kai‐Hung Israel Journal of Chemistry, Vol. 63, Issue 7-8 https://doi.org/10.1002/ijch.202300034	journal	March 2023
Preclinical Studies of Noncharged Oxime Reactivators for Organophosphate Exposure: NONCHARGED OXIME REACTIVATORS Okolotowicz, Karl J.; Dwyer, Mary; Smith, Emily Journal of Biochemical and Molecular Toxicology, Vol. 28, Issue 1 https://doi.org/10.1002/jbt.21519	journal	August 2013
Biomonitoring of Exposure to Chemical Warfare Agents: A Review Noort, D.; Benschop, H. P.; Black, R. M. Toxicology and Applied Pharmacology, Vol. 184, Issue 2 https://doi.org/10.1006/taap.2002.9449	journal	October 2002
Reactivation kinetics of acetylcholinesterase from different species inhibited by highly toxic organophosphates F., Worek; G., Reiter; P., Eyer Archives of Toxicology, Vol. 76, Issue 9 https://doi.org/10.1007/s00204-002-0375-1	journal	September 2002
Organophosphorus compounds and oximes: a critical review Worek, Franz; Thiermann, Horst; Wille, Timo Archives of Toxicology, Vol. 94, Issue 7 https://doi.org/10.1007/s00204-020-02797-0	journal	June 2020
Are the current commercially available oximes capable of reactivating acetylcholinesterase inhibited by the nerve agents of the A-series? Santos, Marcelo C.; Botelho, Fernanda D.; Gonçalves, Arlan S. Archives of Toxicology, Vol. 96, Issue 9 https://doi.org/10.1007/s00204-022-03316-z	journal	June 2022
A-agents, misleadingly known as “Novichoks”: a narrative review Opravil, Jakub; Pejchal, Jaroslav; Finger, Vladimir Archives of Toxicology, Vol. 97, Issue 10 https://doi.org/10.1007/s00204-023-03571-8	journal	August 2023
A-series agent A-234: initial in vitro and in vivo characterization Hrabinova, Martina; Pejchal, Jaroslav; Hepnarova, Vendula Archives of Toxicology, Vol. 98, Issue 4 https://doi.org/10.1007/s00204-024-03689-3	journal	March 2024
Purification and properties of butyrylcholinesterase from horse serum Lee, James C.; Harpst, Jerry A. Archives of Biochemistry and Biophysics, Vol. 145, Issue 1 https://doi.org/10.1016/0003-9861(71)90009-9	journal	July 1971
New substrates of acetylcholinesterase Naveh, Meira; Bernstein, Zmira; Segal, Dina FEBS Letters, Vol. 134, Issue 1 https://doi.org/10.1016/0014-5793(81)80549-2	journal	November 1981
Oxime Reactivation of Diethylphosphoryl Human Serum Cholinesterase Wang, E. I. C.; Braid, P. E. Journal of Biological Chemistry, Vol. 242, Issue 11 https://doi.org/10.1016/S0021-9258(18)99623-7	journal	June 1967
Novichok nerve agent poisoning Steindl, David; Boehmerle, Wolfgang; Körner, Roland The Lancet, Vol. 397, Issue 10270 https://doi.org/10.1016/S0140-6736(20)32644-1	journal	January 2021
Organophosphorus poisoning: the wet opioid toxidrome Eddleston, Michael; Chowdhury, Fazle Rabbi The Lancet, Vol. 397, Issue 10270 https://doi.org/10.1016/S0140-6736(20)32749-5	journal	January 2021
Limitation of the Ellman method: Cholinesterase activity measurement in the presence of oximes Šinko, Goran; Čalić, Maja; Bosak, Anita Analytical Biochemistry, Vol. 370, Issue 2 https://doi.org/10.1016/j.ab.2007.07.023	journal	November 2007
Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes Worek, Franz; Thiermann, Horst; Szinicz, Ladislaus Biochemical Pharmacology, Vol. 68, Issue 11 https://doi.org/10.1016/j.bcp.2004.07.038	journal	December 2004
Crystal structures of acetylcholinesterase in complex with HI-6, Ortho-7 and obidoxime: Structural basis for differences in the ability to reactivate tabun conjugates Ekström, Fredrik; Pang, Yuan-Ping; Boman, Malin Biochemical Pharmacology, Vol. 72, Issue 5 https://doi.org/10.1016/j.bcp.2006.05.027	journal	August 2006
Kinetic analysis of reactivation and aging of human acetylcholinesterase inhibited by different phosphoramidates Worek, Franz; Aurbek, Nadine; Koller, Marianne Biochemical Pharmacology, Vol. 73, Issue 11 https://doi.org/10.1016/j.bcp.2007.02.008	journal	June 2007
Bisquaternary pyridinium oximes: Comparison of in vitro reactivation potency of compounds bearing aliphatic linkers and heteroaromatic linkers for paraoxon-inhibited electric eel and recombinant human acetylcholinesterase Bharate, Sandip B.; Guo, Lilu; Reeves, Tony E. Bioorganic & Medicinal Chemistry, Vol. 18, Issue 2 https://doi.org/10.1016/j.bmc.2009.11.052	journal	January 2010
Comparison of oxime reactivation and aging of nerve agent-inhibited monkey and human acetylcholinesterases Luo, Chunyuan; Tong, Min; Maxwell, Donald M. Chemico-Biological Interactions, Vol. 175, Issue 1-3 https://doi.org/10.1016/j.cbi.2008.04.034	journal	September 2008
Acetylcholinesterase: From 3D structure to function Dvir, Hay; Silman, Israel; Harel, Michal Chemico-Biological Interactions, Vol. 187, Issue 1-3 https://doi.org/10.1016/j.cbi.2010.01.042	journal	September 2010
Post-exposure treatment with the oxime RS194B rapidly reverses early and advanced symptoms in macaques exposed to sarin vapor Rosenberg, Yvonne J.; Mao, Lingjun; Jiang, Xiaoming Chemico-Biological Interactions, Vol. 274 https://doi.org/10.1016/j.cbi.2017.07.003	journal	August 2017
Synthesis and in vitro evaluation of neutral aryloximes as reactivators of Electrophorus eel acetylcholinesterase inhibited by NEMP, a VX surrogate Cavalcante, Samir F. de A.; Kitagawa, Daniel A. S.; Rodrigues, Rafael B. Chemico-Biological Interactions, Vol. 309 https://doi.org/10.1016/j.cbi.2019.05.048	journal	August 2019
Theoretical assessment of the performances of commercial oximes on the reactivation of acetylcholinesterase inhibited by the nerve agent A-242 (novichok) Santos, Marcelo C.; Botelho, Fernanda D.; Gonçalves, Arlan S. Food and Chemical Toxicology, Vol. 165 https://doi.org/10.1016/j.fct.2022.113084	journal	July 2022
Oxime-mediated reactivation of organophosphate-inhibited acetylcholinesterase with emphasis on centrally-active oximes Chambers, Janice E.; Dail, Mary B.; Meek, Edward C. Neuropharmacology, Vol. 175 https://doi.org/10.1016/j.neuropharm.2020.108201	journal	September 2020
A novel muscarinic receptor-based cellular bioanalytical method for sensitive detection and differentiation of highly toxic organophosphorus compounds Ma, Bo; Li, Zhi; Xu, Hua Sensors and Actuators B: Chemical, Vol. 441 https://doi.org/10.1016/j.snb.2025.137982	journal	October 2025
Reactivation of organophosphate-inhibited human, Cynomolgus monkey, swine and guinea pig acetylcholinesterase by MMB-4: A modified kinetic approach Worek, Franz; Wille, Timo; Aurbek, Nadine Toxicology and Applied Pharmacology, Vol. 249, Issue 3 https://doi.org/10.1016/j.taap.2010.09.021	journal	December 2010
Improved chemical synthesis, identification and evaluation of prospective centrally active oxime antidotes for the treatment of nerve agent exposure Valdez, Carlos A.; Lam, Doris; Lao, Victoria Tetrahedron, Vol. 144 https://doi.org/10.1016/j.tet.2023.133598	journal	September 2023
Analysis of inhibition, reactivation and aging kinetics of highly toxic organophosphorus compounds with human and pig acetylcholinesterase Aurbek, N.; Thiermann, H.; Szinicz, L. Toxicology, Vol. 224, Issue 1-2 https://doi.org/10.1016/j.tox.2006.04.030	journal	July 2006
Enzyme-kinetic investigation of different sarin analogues reacting with human acetylcholinesterase and butyrylcholinesterase Bartling, A.; Worek, F.; Szinicz, L. Toxicology, Vol. 233, Issue 1-3 https://doi.org/10.1016/j.tox.2006.07.003	journal	April 2007
Inhibition, reactivation and aging kinetics of highly toxic organophosphorus compounds: Pig versus minipig acetylcholinesterase Worek, F.; Aurbek, N.; Wetherell, J. Toxicology, Vol. 244, Issue 1 https://doi.org/10.1016/j.tox.2007.10.021	journal	February 2008
Comparative protective effects of HI-6 and MMB-4 against organophosphorous nerve agent poisoning Lundy, Paul M.; Hamilton, Murray G.; Sawyer, Thomas W. Toxicology, Vol. 285, Issue 3 https://doi.org/10.1016/j.tox.2011.04.006	journal	July 2011
Hydrolysis of an acetylthiocholine by pralidoxime iodide (2-PAM) Sakurada, Koichi; Ikegaya, Hiroshi; Ohta, Hikoto Toxicology Letters, Vol. 166, Issue 3 https://doi.org/10.1016/j.toxlet.2006.07.339	journal	October 2006
Cholinesterase pseudo-activity, oximolysis, esterolysis, thiocholine ester hydrolysis by oximes: What's in a name? Petroianu, G. Toxicology Letters, Vol. 168, Issue 1 https://doi.org/10.1016/j.toxlet.2006.10.007	journal	January 2007
Investigation of the reactivation kinetics of a large series of bispyridinium oximes with organophosphate-inhibited human acetylcholinesterase Winter, Michael; Wille, Timo; Musilek, Kamil Toxicology Letters, Vol. 244 https://doi.org/10.1016/j.toxlet.2015.07.007	journal	February 2016
Desorption Electrospray Ionization Mass Spectrometry: 20 Years Morato, Nicolás M.; Cooks, R. Graham Accounts of Chemical Research, Vol. 56, Issue 18 https://doi.org/10.1021/acs.accounts.3c00382	journal	September 2023
Acoustic Mist Ionization-Mass Spectrometry: A Comparison to Conventional High-Throughput Screening and Compound Profiling Platforms Belov, Arseniy M.; Kozole, Joseph; Bean, Mark F. Analytical Chemistry, Vol. 92, Issue 20 https://doi.org/10.1021/acs.analchem.0c02508	journal	September 2020
High-Throughput Label-Free Biochemical Assays Using Infrared Matrix-Assisted Desorption Electrospray Ionization Mass Spectrometry Pu, Fan; Radosevich, Andrew J.; Sawicki, James W. Analytical Chemistry, Vol. 93, Issue 17 https://doi.org/10.1021/acs.analchem.1c00737	journal	April 2021
Ultra-High-Throughput Ambient MS: Direct Analysis at 22 Samples per Second by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry Radosevich, Andrew J.; Pu, Fan; Chang-Yen, David Analytical Chemistry, Vol. 94, Issue 12 https://doi.org/10.1021/acs.analchem.1c04605	journal	March 2022
Online Monitoring of Enzymatic Reactions Using Time-Resolved Desorption Electrospray Ionization Mass Spectrometry Cheng, Si; Wu, Qiuhua; Xiao, He Analytical Chemistry, Vol. 89, Issue 4 https://doi.org/10.1021/acs.analchem.6b03975	journal	January 2017
High-Throughput Nanoelectrospray Ionization-Mass Spectrometry Analysis of Microfluidic Droplet Samples Steyer, Daniel J.; Kennedy, Robert T. Analytical Chemistry, Vol. 91, Issue 10 https://doi.org/10.1021/acs.analchem.9b00571	journal	April 2019
Nerve Agents: What They Are, How They Work, How to Counter Them Costanzi, Stefano; Machado, John-Hanson; Mitchell, Moriah ACS Chemical Neuroscience, Vol. 9, Issue 5 https://doi.org/10.1021/acschemneuro.8b00148	journal	January 2018
High-Throughput Assessment of Bile Salt Export Pump Inhibition Using RapidFire-MS and DESI-MS Li, Jie; Morato, Nicolás M.; Westover, Lori S. ACS Medicinal Chemistry Letters, Vol. 15, Issue 9 https://doi.org/10.1021/acsmedchemlett.4c00302	journal	August 2024
Recording spectrophotometric method for determination of dissociation and phosphorylation constants for the inhibition of acetylcholinesterase by organophosphates in the presence of substrate Hart, Geoffrey J.; O'Brien, Richard D. Biochemistry, Vol. 12, Issue 15 https://doi.org/10.1021/bi00739a026	journal	July 1973
Does “Butyrylization” of Acetylcholinesterase through Substitution of the Six Divergent Aromatic Amino Acids in the Active Center Gorge Generate an Enzyme Mimic of Butyrylcholinesterase? Kaplan, Dana; Ordentlich, Arie; Barak, Dov Biochemistry, Vol. 40, Issue 25 https://doi.org/10.1021/bi010181x	journal	May 2001
An In Vitro Comparative Study on the Reactivation of Nerve Agent-Inhibited Guinea Pig and Human Acetylcholinesterases by Oximes Luo, Chunyuan; Tong, Min; Chilukuri, Nageswararao Biochemistry, Vol. 46, Issue 42 https://doi.org/10.1021/bi701002f	journal	September 2007
The pH Dependence of Dealkylation in Soman-Inhibited Cholinesterases and Their Mutants: Further Evidence for a Push−Pull Mechanism Saxena, Ashima; Viragh, Carol; Frazier, D. Scott Biochemistry, Vol. 37, Issue 43 https://doi.org/10.1021/bi980917z	journal	October 1998
Rapid Exploration of Chemical Space by High-Throughput Desorption Electrospray Ionization Mass Spectrometry Huang, Kai-Hung; Morato, Nicolás M.; Feng, Yunfei Journal of the American Chemical Society, Vol. 146, Issue 48 https://doi.org/10.1021/jacs.4c11037	journal	November 2024
Amidine−Oximes: Reactivators for Organophosphate Exposure Kalisiak, Jarosław; Ralph, Erik C.; Zhang, Jun Journal of Medicinal Chemistry, Vol. 54, Issue 9 https://doi.org/10.1021/jm200054r	journal	May 2011
Acetylcholinesterase — new roles for an old actor Soreq, Hermona; Seidman, Shlomo Nature Reviews Neuroscience, Vol. 2, Issue 4 https://doi.org/10.1038/35067589	journal	April 2001
Differential binding of bispyridinium oxime drugs with acetylcholinesterase Kesharwani, Manoj K.; Ganguly, Bishwajit; Das, Amit Acta Pharmacologica Sinica, Vol. 31, Issue 3 https://doi.org/10.1038/aps.2009.193	journal	February 2010
High-throughput matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry–based deubiquitylating enzyme assay for drug discovery De Cesare, Virginia; Moran, Jennifer; Traynor, Ryan Nature Protocols, Vol. 15, Issue 12 https://doi.org/10.1038/s41596-020-00405-0	journal	November 2020
Development of a CNS-permeable reactivator for nerve agent exposure: an iterative, multi-disciplinary approach Bennion, Brian J.; Malfatti, Michael A.; Be, Nicholas A. Scientific Reports, Vol. 11, Issue 1 https://doi.org/10.1038/s41598-021-94963-2	journal	July 2021
High-throughput screening of organic reactions in microdroplets using desorption electrospray ionization mass spectrometry (DESI-MS): hardware and software implementation Sobreira, Tiago Jose P.; Avramova, Larisa; Szilagyi, Botond Analytical Methods, Vol. 12, Issue 28 https://doi.org/10.1039/D0AY00072H	journal	January 2020
High-throughput screening by droplet microfluidics: perspective into key challenges and future prospects Payne, Emory M.; Holland-Moritz, Daniel A.; Sun, Shuwen Lab on a Chip, Vol. 20, Issue 13 https://doi.org/10.1039/D0LC00347F	journal	January 2020
High-throughput label-free opioid receptor binding assays using an automated desorption electrospray ionization mass spectrometry platform Feng, Yunfei; Morato, Nicolás M.; Huang, Kai-Hung Chemical Communications, Vol. 60, Issue 63 https://doi.org/10.1039/D4CC02346C	journal	January 2024
High-throughput microdroplet-based synthesis using automated array-to-array transfer Huang, Kai-Hung; Chen, Kitmin; Morato, Nicolás M. Chemical Science, Vol. 16, Issue 17 https://doi.org/10.1039/D5SC00638D	journal	January 2025
High activity of human butyrylcholinesterase at low pH in the presence of excess butyrylthiocholine Masson, Patrick; Nachon, Florian; Bartels, Cynthia F. European Journal of Biochemistry, Vol. 270, Issue 2 https://doi.org/10.1046/j.1432-1033.2003.03388.x	journal	December 2002
The Butyrylcholinesterase K‐Variant Shows Similar Cellular Protein Turnover and Quaternary Interaction to the Wild‐Type Enzyme Altamirano, Cibby Varkey; Bartels, Cynthia F.; Lockridge, Oksana Journal of Neurochemistry, Vol. 74, Issue 2 https://doi.org/10.1046/j.1471-4159.2000.740869.x	journal	February 2000
New Structural Scaffolds for Centrally Acting Oxime Reactivators of Phosphylated Cholinesterases Sit, Rakesh K.; Radić, Zoran; Gerardi, Valeria Journal of Biological Chemistry, Vol. 286, Issue 22 https://doi.org/10.1074/jbc.M111.230656	journal	April 2011
Refinement of Structural Leads for Centrally Acting Oxime Reactivators of Phosphylated Cholinesterases Radić, Zoran; Sit, Rakesh K.; Kovarik, Zrinka Journal of Biological Chemistry, Vol. 287, Issue 15 https://doi.org/10.1074/jbc.M111.333732	journal	February 2012
Strengthening controls on Novichoks: a family-based approach to covering A-series agents and precursors under the chemical-weapons nonproliferation regime Costanzi, Stefano; Koblentz, Gregory D. The Nonproliferation Review, Vol. 28, Issue 1-3 https://doi.org/10.1080/10736700.2021.2020010	journal	June 2021
Novichok: a murderous nerve agent attack in the UK Vale, J. Allister; Marrs, Timothy C.; Maynard, Robert L. Clinical Toxicology, Vol. 56, Issue 11 https://doi.org/10.1080/15563650.2018.1469759	journal	May 2018
Synthesis and In Vitro and In Vivo Inhibition Potencies of Highly Relevant Nerve Agent Surrogates Meek, Edward C.; Chambers, Howard W.; Coban, Alper Toxicological Sciences, Vol. 126, Issue 2 https://doi.org/10.1093/toxsci/kfs013	journal	January 2012
Theoretical study of the molecular aspect of the suspected novichok agent A234 of the Skripal poisoning Bhakhoa, Hanusha; Rhyman, Lydia; Ramasami, Ponnadurai Royal Society Open Science, Vol. 6, Issue 2 https://doi.org/10.1098/rsos.181831	journal	February 2019
Theoretical study on the toxicity of ‘Novichok’ agent candidates Jeong, Keunhong; Choi, Junwon Royal Society Open Science, Vol. 6, Issue 8 https://doi.org/10.1098/rsos.190414	journal	August 2019
Kinetics for the inhibition of acetylcholinesterase from the electric eel by some organophosphates and carbamates Forsberg, Ake; Puu, Gertrud European Journal of Biochemistry, Vol. 140, Issue 1 https://doi.org/10.1111/j.1432-1033.1984.tb08079.x	journal	April 1984
Mass Spectrometry Sampling Under Ambient Conditions with Desorption Electrospray Ionization Takats, Z. Science, Vol. 306, Issue 5695, p. 471-473 https://doi.org/10.1126/science.1104404	journal	October 2004
Automated High-Throughput System Combining Small-Scale Synthesis with Bioassays and Reaction Screening Morato, Nicolás M.; Le, MyPhuong T.; Holden, Dylan T. SLAS Technology, Vol. 26, Issue 6 https://doi.org/10.1177/24726303211047839	journal	December 2021
Development of the Bisquaternary Oxime HI-6 Toward Clinical Use in the Treatment of Organophosphate Nerve Agent Poisoning Lundy, Paul M.; Raveh, Lily; Amitai, Gabriel Toxicological Reviews, Vol. 25, Issue 4 https://doi.org/10.2165/00139709-200625040-00004	journal	January 2006
Pyridinium Oximes as Cholinesterase Reactivators. Structure-Activity Relationship and Efficacy in the Treatment of Poisoning with Organophosphorus Compounds Jokanovic, Milan; Prostran, Milica Current Medicinal Chemistry, Vol. 16, Issue 17 https://doi.org/10.2174/092986709788612729	journal	June 2009
Nerve Agents’ Surrogates: Invaluable Tools for Development of Acetylcholinesterase Reactivators de A. Cavalcante, Samir F.; Simas, Alessandro B. C.; Kuča, Kamil Current Organic Chemistry, Vol. 23, Issue 14 https://doi.org/10.2174/1385272823666190806114017	journal	October 2019

Similar Records

Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin

Journal Article · Thu Oct 28 04:00:00 UTC 2010 · Mol. Pharmacol. · OSTI ID:1002825

Hemmert, Andrew C; Otto, Tamara C; Wierdl, Monika; +7 more

Structural and dynamic effects of paraoxon binding to human acetylcholinesterase by X-ray crystallography and inelastic neutron scattering

Journal Article · Wed Oct 19 00:00:00 UTC 2022 · Structure · OSTI ID:1897837

Gerlits, Oksana; Fajer, Mikolai; Cheng, Xiaolin; +3 more

Kinetic and structural evidence for specific DMSO interference with reversible binding of uncharged bis-oximes to hAChE and their reactivation kinetics of OP-hAChE

Journal Article · Fri Jul 11 00:00:00 UTC 2025 · Chemico-Biological Interactions · OSTI ID:3002291

Kolić, Dora; Gerlits, Oksana; Kucharski, Megan; +4 more

Related Subjects

acetylcholinesterase
enzyme inhibition
mass spectrometry
medical countermeasures

Title: Accelerating countermeasure candidate discovery for A-series chemical warfare agent exposure

Citation Formats

References (76)

Similar Records

Related Subjects