title: Sunitinib, a Clinically Used Anticancer Drug, Is a Potent AChE Inhibitor and Attenuates Cognitive Impairments in Mice.
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.
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.|Ningbo Kangning Hospital, Ningbo, Zhejiang 315200, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Lin
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Siying
authors.initials: S
authors.lastname: Xiang
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Kangrong
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Applied Biology and Chemistry Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University , Hong Kong SAR, China.
authors.forename: Daping
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Applied Biology and Chemistry Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University , Hong Kong SAR, China.
authors.forename: Shinghung
authors.initials: S
authors.lastname: Mak
authors.affiliation: Department of Applied Biology and Chemistry Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University , Hong Kong SAR, China.
authors.forename: Shengquan
authors.initials: S
authors.lastname: Hu
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Shehani
authors.initials: S
authors.lastname: Nirasha
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Zaijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315200, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Applied Biology and Chemistry Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University , Hong Kong SAR, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315200, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University , Ningbo, Zhejiang 315211, China.
authors.forename: Qinwen
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy*; D004195:Disease Models, Animal; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D007189:Indans / Q000494:pharmacology; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D062105:Molecular Docking Simulation; D010880:Piperidines / Q000494:pharmacology; D011758:Pyrroles / Q000627:therapeutic use*; D012601:Scopolamine / Q000633:toxicity; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D007189:Indans; D007211:Indoles; D010880:Piperidines; D011758:Pyrroles; D000077265:Donepezil; D012601:Scopolamine; D000110:Acetylcholinesterase; D000077210:Sunitinib
keywords: AChE; Alzheimer’s disease; cancer; cognitive impairments; sunitinib