期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 134, 期 -, 页码 24-33出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2017.04.004
关键词
PTP1B; Bromophenol; Saccharide; Selectivity; Permeability
资金
- National Natural Science Foundation of China [41506169]
- Key research and development project of Shandong province [2015GSF115029, 2016ZDJS07A13]
- Project of Discovery, Evaluation and Transformation of Active Natural Compounds, Strategic Biological Resources Service Network Programme of Chinese Academy of Sciences [ZSTH-026]
- Qingdao National Laboratory for Marine Science and Technology [2015ASKJ02, 2015ASTP]
Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signaling pathway. Inhibition of PTP1B is expected to improve insulin action. Appropriate selectivity and permeability are the gold standard for excellent PTP1B inhibitors. In this work, molecular hybridization-based screening identified a selective competitive PTP1B inhibitor. Compound 10a has IC50 values of 199 nM against PTP1B, and shows 32-fold selectivity for PTP1B over the closely related phosphatase TCPTP). Molecule docking and molecular dynamics studies reveal the reason of selectivity for PTP1B over TCPTP. Moreover, the cell permeability and cellular activity of compound 10a are demonstrated respectively. (C) 2017 Elsevier Masson SAS. All rights reserved.
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