Oleanolic acid and its derivatives: New inhibitor of protein tyrosine phosphatase 1B with cellular activities

被引：138

作者：

Zhang, Yi-Nan ^{[2
]}

Zhang, Wei ^{[1
]}

Hong, Di ^{[2
]}

Shi, Lei ^{[1
]}

Shen, Qiang ^{[1
]}

Li, Jing-Ya ^{[1
]}

Li, Jia ^{[1
]}

Hu, Li-Hong ^{[2
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Shanghai Res Ctr Modernizat Tradit Chinese Med, Shanghai 201203, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 18期

基金：

中国国家自然科学基金;

关键词：

protein tyrosine phosphatase 1B; oleanolic acid; inhibitor; SAR (structure-activity relationship);

D O I：

10.1016/j.bmc.2008.07.080

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Protein tyrosine phosphatase 1B is a key factor in the negative regulation of insulin pathway and a promising target for treatment of diabetes and obesity. Herein, a series of competitive inhibitors were optimized from oleanolic acid, a natural triterpenoid identified against PTP1B by screening libraries of traditional Chinese medicinal herbs. Modifying at 3 and 28 positions, we obtained compound 13 with a K-i of 130 nM, which exhibited good selectivity between other phosphatases involved in insulin pathway except T-cell protein tyrosine phosphatase. Further evaluation in cell models illustrated that the derivatives enhanced insulin receptor phosphorylation in CHO/hIR cells and also stimulated glucose uptake in L6 myotubes with or addition of without insulin. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：8697 / 8705

页数：9

共 40 条

[1] CRYSTAL-STRUCTURE OF HUMAN PROTEIN-TYROSINE-PHOSPHATASE 1B [J].