Dimethyl sulfoxide (DMSO) is the most common organic solvent used in biochemical and cellular assays during drug discovery programs. Despite its wide use, the effect of DMSO on several enzyme classes, which are crucial targets of the new therapeutic agents, are still unexplored. Here, we report the detailed biochemical analysis of the effects of DMSO on the human acetylcholine-degrading enzyme, acetylcholinesterase (AChE), the primary target of current Alzheimer’s therapeutics. Our analysis showed that DMSO is a considerably potent and highly selective irreversible mixed-competitive inhibitor of human AChE with IC₅₀ values in the lower millimolar range, corresponding to 0.88% to 2.6% DMSO (v/v). Most importantly, 1–4% (v/v) DMSO, the commonly used experimental concentrations, showed ∼37–80% inhibition of human AChE activity. We believe that our results will assist in developing stringent protocols and help in the better interpretation of experimental outcomes during screening and biological evaluation of new drugs.

中文翻译：

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DMSO：人乙酰胆碱酯酶的混合竞争抑制剂

二甲基亚砜（DMSO）是药物发现计划期间用于生化和细胞分析的最常见有机溶剂。尽管其广泛使用，DMSO对几种酶类的作用仍是一种新的治疗靶标，而DMSO是新治疗剂的关键靶标。在这里，我们报告了DMSO对人乙酰胆碱降解酶，乙酰胆碱酯酶（AChE）（当前阿尔茨海默氏病治疗的主要目标）的影响的详细生化分析。我们的分析表明，DMSO是具有IC ₅₀的人类AChE的强效且高度选择性的不可逆混合竞争抑制剂。值在较低的毫摩尔范围内，对应于0.88％至2.6％的DMSO（v / v）。最重要的是，通常使用的实验浓度1-4％（v / v）DMSO对人的AChE活性显示出约37-80％的抑制作用。我们相信我们的结果将有助于制定严格的方案，并有助于在新药的筛选和生物学评估过程中更好地解释实验结果。