The article presents a comprehensive study on the nerve agent A-234, a new generation of chemical weapons. The research, conducted by a team from various Czech institutions, focuses on the stability, inhibitory potential, reactivation capability, acute toxicity, and therapeutic effects of A-234. Key findings include: 1. **Stability**: A-234 shows slow hydrolysis in neutral pH, with a residual concentration of 86.2% after 72 hours. 2. **Inhibitory Potential**: A-234 is a potent inhibitor of human acetylcholinesterase (HssAChE) and butyrylcholinesterase (HssBChE), with IC50 values of 0.101 μM and 0.036 μM, respectively. 3. **Reactivation**: Five marketed oximes (HI-6, obidoxime, pralidoxime, methoxime, and trimedoxime) show negligible reactivation ability towards A-234-inhibited HssAChE and HssBChE. 4. **Acute Toxicity**: A-234's toxicity is comparable to that of VX, with atropine and diazepam effectively mitigating its lethality. 5. **Therapeutic Effects**: Atropine and diazepam are effective in reducing muscarinic and nicotinic symptoms, while oximes do not provide significant benefits. HI-6 and methoxime show some positive effects, particularly in reducing tremors. 6. **Molecular Dynamics**: Molecular modeling reveals that all oximes are weak nucleophiles, which may explain their ineffectiveness in reactivating A-234. The study provides essential preclinical data on A-234, highlighting its high stability, toxicity, and resistance to current antidotes. The findings underscore the need for further research to develop more effective treatments for A-series nerve agents.The article presents a comprehensive study on the nerve agent A-234, a new generation of chemical weapons. The research, conducted by a team from various Czech institutions, focuses on the stability, inhibitory potential, reactivation capability, acute toxicity, and therapeutic effects of A-234. Key findings include: 1. **Stability**: A-234 shows slow hydrolysis in neutral pH, with a residual concentration of 86.2% after 72 hours. 2. **Inhibitory Potential**: A-234 is a potent inhibitor of human acetylcholinesterase (HssAChE) and butyrylcholinesterase (HssBChE), with IC50 values of 0.101 μM and 0.036 μM, respectively. 3. **Reactivation**: Five marketed oximes (HI-6, obidoxime, pralidoxime, methoxime, and trimedoxime) show negligible reactivation ability towards A-234-inhibited HssAChE and HssBChE. 4. **Acute Toxicity**: A-234's toxicity is comparable to that of VX, with atropine and diazepam effectively mitigating its lethality. 5. **Therapeutic Effects**: Atropine and diazepam are effective in reducing muscarinic and nicotinic symptoms, while oximes do not provide significant benefits. HI-6 and methoxime show some positive effects, particularly in reducing tremors. 6. **Molecular Dynamics**: Molecular modeling reveals that all oximes are weak nucleophiles, which may explain their ineffectiveness in reactivating A-234. The study provides essential preclinical data on A-234, highlighting its high stability, toxicity, and resistance to current antidotes. The findings underscore the need for further research to develop more effective treatments for A-series nerve agents.