Characterization of covalent binding of tyrosine kinase inhibitors to plasma proteins

doi:10.1016/j.dmpk.2020.07.002

	Characterization of covalent binding of tyrosine kinase inhibitors to plasma proteins
	Liu, Xiaoyun 1,2; Feng, Dan 1,3; Zheng, Mingyue 1,2; Cui, Yongmei 3; Zhong, Dafang 1,2
刊名	DRUG METABOLISM AND PHARMACOKINETICS
	2020-10-01
卷号	35 期号:5 页码:456-465
关键词	Covalent tyrosine kinase inhibitors Covalent binding Human serum albumin Molecular docking Quantitative calculations Linear modeling Species difference
ISSN号	1347-4367
DOI	10.1016/j.dmpk.2020.07.002
通讯作者	Zhong, Dafang(dfzhong@simm.ac.cn)
英文摘要	Eight covalent tyrosine kinase inhibitors (TKIs) were investigated to determine the characteristics of their covalent binding to plasma proteins. The data revealed that their covalent binding to plasma proteins is of species difference. In addition to the reports on neratinib and pyrotinib, osimertinib, alflutinib, AST5902, and ibrutinib were confirmed to covalently bind to the Lys-190 of human serum albumin (HSA). Molecular docking was used to simulate the binding mode of TKIs to HSA. The results exhibited the non-covalent interactions between covalent TKIs and HSA, which stabilize the TKIs-HSA complex and explain the selectivity of covalent binding. The t(1/2) values of TKIs that are covalently bound to HSA or human plasma proteins were studied in vitro, and the features highly correlated with the t(1/2) were determined by quantitative calculations and linear modeling. Reversibility of the covalent binding and the factors affecting the process of reversibility were evaluated. In conclusion, acrylamide moiety of covalent TKIs can covalently bind to lysine residue of HSA, most of which were determined to be Lys-190. The covalent binding is of species difference, especially between animal and human. Except for osimertinib, covalent binding between TKIs and HSA are reversible. (C) 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.
资助项目	National Natural Science Foundation of China[81521005] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050306]
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	JAPANESE SOC STUDY XENOBIOTICS
WOS记录号	WOS:000575073000007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291329]
专题	中国科学院上海药物研究所
通讯作者	Zhong, Dafang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Shanghai Univ, Dept Chem, Shanghai 200444, Peoples R China
推荐引用方式 GB/T 7714	Liu, Xiaoyun,Feng, Dan,Zheng, Mingyue,et al. Characterization of covalent binding of tyrosine kinase inhibitors to plasma proteins[J]. DRUG METABOLISM AND PHARMACOKINETICS,2020,35(5):456-465.
APA	Liu, Xiaoyun,Feng, Dan,Zheng, Mingyue,Cui, Yongmei,&Zhong, Dafang.(2020).Characterization of covalent binding of tyrosine kinase inhibitors to plasma proteins.DRUG METABOLISM AND PHARMACOKINETICS,35(5),456-465.
MLA	Liu, Xiaoyun,et al."Characterization of covalent binding of tyrosine kinase inhibitors to plasma proteins".DRUG METABOLISM AND PHARMACOKINETICS 35.5(2020):456-465.