Plasiatine, an Unprecedented Indole-Phenylpropanoid Hybrid from Plantago asiatica as a Potent Activator of the Nonreceptor Protein Tyrosine Phosphatase Shp2.
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.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, P. R. China.
Zhong-Hua
ZH
Gao
Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510006, P. R. China.
Yi-Ming
YM
Shi
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, P. R. China.
Zhe
Z
Qiang
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, P. R. China.
Xia
X
Wang
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, P. R. China.
Shan-Zhai
SZ
Shang
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, P. R. China.
Yan
Y
Yang
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, P. R. China.
Bao-Wen
BW
Du
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, P. R. China.
Hui-Pan
HP
Peng
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, P. R. China.
Xu
X
Ji
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, P. R. China.
Honglin
H
Li
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, P. R. China.
Fei
F
Wang
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, P. R. China.
Wei-Lie
WL
Xiao
D001688:Biological Products / Q000302:isolation & purification / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D020536:Enzyme Activators / Q000302:isolation & purification / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000302:isolation & purification / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010766:Phosphorylation; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010943:Plantago / Q000737:chemistry*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*; D012639:Seeds / Q000737:chemistry; D013057:Spectrum Analysis
D001688:Biological Products; D020536:Enzyme Activators; D007211:Indoles; D010936:Plant Extracts; D048049:Extracellular Signal-Regulated MAP Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11