Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B

doi:10.1016/j.ejmech.2017.05.007

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	Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B
	Li, Xiang-Qian 1,2; Xu, Qi 1,2,3; Luo, Jiao 1,2,3; Wang, Li-Jun 1,2; Jiang, Bo 1,2; Zhang, Ren-Shuai 1,2; Shi, Da-Yong 1,2,3
	2017-08-18
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷号	136 页码:348-359
文章类型	Article
摘要	Protein tyrosine phosphatases 1B (PTP1B) is a promising and validated therapeutic target to effectively treat T2DM and obesity. However, the development of charged PTP1B inhibitors was restricted due to their low cell permeability and poor bioavailability. Based on active natural products, two series of uncharged catechol derivatives were identified as PTP1B inhibitors by targeting a secondary aryl phosphate-binding site as well as the catalytic site. The most potent inhibitor 22 showed an IC50 of 0.487 mu M against PTP1B and strong selectivity (27-fold) over TCPTP. Kinetic studies were also performed that 22 act as a competitive PTP1B inhibitor. The treatment of C2C12 myotubes with 22 markedly increased the phosphorylation levels of IR beta, Akt and IRS1 phosphorylation. The similarity of its action profiling with that produced by insulin suggested its potential as a new non-insulin-dependent drug candidate. (C) 2017 Elsevier Masson SAS. All rights reserved.
关键词	Type 2 Diabetes Ptp1b Inhibition Selectivity Competitive Cellular Activity
DOI	10.1016/j.ejmech.2017.05.007
收录类别	SCI
语种	英语
WOS记录号	WOS:000403993500029
引用统计	被引频次：19[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
版本	出版稿
条目标识符	http://ir.qdio.ac.cn/handle/337002/137139
专题	实验海洋生物学重点实验室
作者单位	1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao, Peoples R China 2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China
第一作者单位	中国科学院海洋研究所
推荐引用方式 GB/T 7714	Li, Xiang-Qian,Xu, Qi,Luo, Jiao,et al. Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,136:348-359.
APA	Li, Xiang-Qian.,Xu, Qi.,Luo, Jiao.,Wang, Li-Jun.,Jiang, Bo.,...&Shi, Da-Yong.(2017).Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,136,348-359.
MLA	Li, Xiang-Qian,et al."Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 136(2017):348-359.

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