Kumar Amit, Darreh-Shori Taher
Karolinska Institutet , Center for Alzheimer Research, Department of Neurobiology, Care Sciences, and Society, Division of Translational Alzheimer Neurobiology, NOVUM, 4th Floor, 141 86 Stockholm, Sweden.
ACS Chem Neurosci. 2017 Dec 20;8(12):2618-2625. doi: 10.1021/acschemneuro.7b00344. Epub 2017 Oct 16.
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 IC 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.
二甲基亚砜（DMSO）是药物研发项目中生物化学和细胞分析中最常用的有机溶剂。尽管其应用广泛，但DMSO对几种酶类的影响仍未得到探索，而这些酶类是新型治疗药物的关键靶点。在此，我们报告了DMSO对人类乙酰胆碱降解酶乙酰胆碱酯酶（AChE）影响的详细生化分析，AChE是当前阿尔茨海默病治疗的主要靶点。我们的分析表明，DMSO是一种相当强效且高度选择性的不可逆混合型竞争性人类AChE抑制剂，其IC值处于较低的毫摩尔范围内，相当于0.88%至2.6%的DMSO（体积/体积）。最重要的是，常用的实验浓度1 - 4%（体积/体积）的DMSO对人类AChE活性的抑制率约为37 - 80%。我们相信，我们的结果将有助于制定严格的实验方案，并有助于在新药筛选和生物学评估过程中更好地解释实验结果。
