Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B
文献类型：期刊论文
| 作者 | 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 |
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2017-08-18 |
| 卷号 | 136页码:348-359 |
| 关键词 | Type 2 Diabetes Ptp1b Inhibition Selectivity Competitive Cellular Activity |
| DOI | 10.1016/j.ejmech.2017.05.007 |
| 文献子类 | Article |
| 英文摘要 | 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. |
| 语种 | 英语 |
| WOS记录号 | WOS:000403993500029 |
| 版本 | 出版稿 |
| 源URL | [http://ir.qdio.ac.cn/handle/337002/137139]  |
| 专题 | 海洋研究所_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 |
| 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. |
入库方式： OAI收割
来源：海洋研究所
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