Oleanolic acid and its derivatives: New inhibitor of protein tyrosine phosphatase 1B with cellular activities
Oleanolic acid and its derivatives: New inhibitor of protein tyrosine phosphatase 1B with cellular activities
复制标题
齐墩果酸及其衍生物：具有细胞活性的新型蛋白酪氨酸磷酸酶1B抑制剂
DOI：
10.1016/j.bmc.2008.07.080
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发表时间：
2008-09-15
影响因子：
3.5
通讯作者：
Hu, Li-Hong
中科院分区：
文献类型：
--
作者：
Zhang, Yi-Nan;Zhang, Wei;Hu, Li-Hong
蛋白酪氨酸磷酸酶1B（Protein tyrosine phosphatase 1B，PTP 1B）是胰岛素途径负调控的关键因子，是治疗糖尿病和肥胖的一个有希望的靶点。本文通过筛选中草药文库，从天然三萜化合物油酸中筛选出一系列抗PTP 1B的竞争性抑制剂。在3位和28位进行修饰，我们获得了具有130 nM的Ki的化合物13，其在除T细胞蛋白酪氨酸磷酸酶之外的参与胰岛素途径的其他磷酸酶之间表现出良好的选择性。在细胞模型中的进一步评价表明，衍生物增强了CHO/hIR细胞中的胰岛素受体磷酸化，并且在有或没有胰岛素的情况下也刺激了L 6肌管中的葡萄糖摄取。(C)2008爱思唯尔有限公司保留所有权利。
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.