65012-07-9Relevant academic research and scientific papers
Anthraquinone derivatives as potent inhibitors of c-Met kinase and the extracellular signaling pathway
Liang, Zhongjie,Ai, Jing,Ding, Xiao,Peng, Xia,Zhang, Dengyou,Zhang, Ruihan,Wang, Ying,Liu, Fang,Zheng, Mingyue,Jiang, Hualiang,Liu, Hong,Geng, Meiyu,Luo, Cheng
supporting information, p. 408 - 413 (2013/06/05)
The aberrant function of c-Met kinase signaling pathway is ubiquitously involved in a broad spectrum of human cancers; thus, a strong rationale exists for targeting the kinase pathway in cancer therapy. Via integration of computational and experimental studies, anthraquinone derivatives were identified for the first time as potent c-Met kinase inhibitors in this research. The aberrant activation of the c-Met kinase pathway results from (TPR)-Met, MET gene mutation, or amplification and a hepatocyte growth factor (HGF)/scatter factor-dependent autocrine or paracrine mechanism. However, anthraquinone derivatives exclusively suppressed c-Met phosphorylation stimulated by HGF in A549 cells, indicating that the compounds possess the ability to block the extracellular HGF-dependent pathway. A surface plasmon resonance assay revealed that the most potent compound, 2a, shows a high binding affinity for HGF with an equilibrium dissociation constant of 1.95 μM. The dual roles of compound 2a demonstrate the potency of anthraquinone derivatives and provide a new design solution for the c-Met kinase signaling pathway.
