Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/62097
Title: Sunitinib, a clinically used anticancer drug, is a potent AChE inhibitor and attenuates cognitive impairments in mice
Authors: Huang, L
Lin, J
Xiang, S
Zhao, K
Yu, J
Zheng, J
Xu, D
Mak, S
Hu, S
Nirasha, S
Wang, C
Chen, X
Zhang, J
Xu, S
Wei, X
Zhang, Z
Zhou, D
Zhou, W
Cui, W
Han, Y 
Hu, Z
Wang, Q
Keywords: AChE
Alzheimer's disease
Cancer
Cognitive impairments
Sunitinib
Issue Date: 2016
Publisher: American Chemical Society
Source: ACS chemical neuroscience, 2016, v. 7, no. 8, p. 1047-1056 How to cite?
Journal: ACS chemical neuroscience 
Abstract: 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.
URI: http://hdl.handle.net/10397/62097
ISSN: 1948-7193
DOI: 10.1021/acschemneuro.5b00329
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