Gao Zhong-Hua, Shi Yi-Ming, Qiang Zhe, Wang Xia, Shang Shan-Zhai, Yang Yan, Du Bao-Wen, Peng Hui-Pan, Ji Xu, Li Honglin, Wang Fei, Xiao Wei-Lie
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, P. R. China.
Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510006, P. R. China.
Sci Rep. 2016 Apr 22;6:24945. doi: 10.1038/srep24945.
Plasiatine (1), isolated from the seeds of Plantago asiatica, is an unprecedented indole analogue linked to a phenylpropanoid moiety via a carbon bond that builds up a novel heteromeric construction with a C19N2 scaffold. Its structure was determined by spectroscopic data and computational evidence. Notably, experimental assay demonstrated that 1 significantly enhanced the activity of the nonreceptor protein tyrosine phosphatase Shp2 in vitro in a concentration-dependent manner with an EC50 value of 0.97 μM, and activated phosphorylation of ERK, a known target of Shp2. Moreover, plasiatine (1) promoted hepatocellular HepG2 cells migration. Molecular docking suggested that plasiatine (1) binds to the catalytic cleft of Shp2. These results identified plasiatine (1) as the first small molecule Shp2 activator, and it warrants further investigation as a novel pharmaceutical tool to study the function of Shp2 in tumorigenesis.
从车前草种子中分离得到的车前草碱（1）是一种前所未有的吲哚类似物，它通过碳键与一个苯丙素部分相连，形成了一种具有C19N2支架的新型异聚结构。其结构由光谱数据和计算证据确定。值得注意的是，实验分析表明，1在体外以浓度依赖的方式显著增强了非受体蛋白酪氨酸磷酸酶Shp2的活性，EC50值为0.97 μM，并激活了Shp2的已知靶点ERK的磷酸化。此外，车前草碱（1）促进了肝癌HepG2细胞的迁移。分子对接表明，车前草碱（1）与Shp2的催化裂隙结合。这些结果确定车前草碱（1）为首个小分子Shp2激活剂，作为研究Shp2在肿瘤发生中功能的新型药物工具，值得进一步研究。
