机构：[1]Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China[2]Ningbo Kangning Hospital, Ningbo, Zhejiang 315200, China[3]Department of Applied Biology and Chemistry Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University, Hong Kong SAR, China[4]Institute of New Drug Research, Guangdong Province Key Laboratory of Pharmacodynamic, Constituents of Traditional Chinese Medicine & New Drug Research, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
Sunitinib, a tyrosine kinase inhibitor, is clinically used for the treatment of cancer. In this study, we found for the first time that sunitinib inhibits acetylcholinesterase (AChE) at submicromolar concentrations in vitro. In addition, sunitinib dramatically decreased the hippocampal and cortical activity of AChE in a time-dependent manner in mice. Molecular docking analysis further demonstrates that sunitinib might interact with both the catalytic anion and peripheral anionic sites within AChE, which is in accordance with enzymatic activity results showing that sunitinib inhibits AChE in a mixed pattern. Most importantly, we evaluated the effects of sunitinib on scopolamine-induced cognitive impairments in mice by using novel object recognition and Morris water maze tests. Surprisingly, sunitinib could attenuate cognitive impairments to a similar extent as donepezil, a marketed AChE inhibitor used for the treatment of Alzheimer's disease. In summary, our results have shown that sunitinib could potently inhibit AChE and attenuate cognitive impairments in mice.
基金：
This work was supported by the Natural Science Foundation of
Zhejiang Province (LY15H310007, LY15090010), Research
Grants Council of Hong Kong (561011 & 15101014), Applied Research Project on Nonprofit Technology of Zhejiang
Province (2016C37110), the National Natural Science
Foundation of China (81202150, 81471398), the Ningbo
international science and technology cooperation project
(2014D10019), 973 Program from the Ministry of Science
and Technology of China (2013CB835100)
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2015]版：
大类|2 区化学
小类|2 区药物化学3 区生化与分子生物学3 区神经科学
最新[2025]版：
大类|3 区医学
小类|2 区生化与分子生物学3 区药物化学3 区神经科学
第一作者：
第一作者机构：[1]Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China[2]Ningbo Kangning Hospital, Ningbo, Zhejiang 315200, China
通讯作者：
推荐引用方式(GB/T 7714)：
Huang Ling,Lin Jiajia,Xiang Siying,et al.Sunitinib, a Clinically Used Anticancer Drug, Is a Potent AChE Inhibitor and Attenuates Cognitive Impairments in Mice.[J].ACS chemical neuroscience.2016,7(8):1047-56.doi:10.1021/acschemneuro.5b00329.
APA：
Huang Ling,Lin Jiajia,Xiang Siying,Zhao Kangrong,Yu Jie...&Wang Qinwen.(2016).Sunitinib, a Clinically Used Anticancer Drug, Is a Potent AChE Inhibitor and Attenuates Cognitive Impairments in Mice..ACS chemical neuroscience,7,(8)
MLA：
Huang Ling,et al."Sunitinib, a Clinically Used Anticancer Drug, Is a Potent AChE Inhibitor and Attenuates Cognitive Impairments in Mice.".ACS chemical neuroscience 7..8(2016):1047-56
