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Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B
Li, Xiang-Qian1,2; Xu, Qi1,2,3; Luo, Jiao1,2,3; Wang, Li-Jun1,2; Jiang, Bo1,2; Zhang, Ren-Shuai1,2; Shi, Da-Yong1,2,3
2017-08-18
Source PublicationEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume136Pages:348-359
SubtypeArticle
AbstractProtein 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.
KeywordType 2 Diabetes Ptp1b Inhibition Selectivity Competitive Cellular Activity
DOI10.1016/j.ejmech.2017.05.007
Indexed BySCI
Language英语
WOS IDWOS:000403993500029
Citation statistics
Cited Times:6[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Version出版稿
Identifierhttp://ir.qdio.ac.cn/handle/337002/137139
Collection实验海洋生物学重点实验室
Affiliation1.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
First Author AffilicationInstitute of Oceanology, Chinese Academy of Sciences
Recommended Citation
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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