Unknown

Dataset Information

0

Anthraquinone Derivatives as Potent Inhibitors of c-Met Kinase and the Extracellular Signaling Pathway.

ABSTRACT: 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 ?M. 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.

SUBMITTER: Liang Z 

PROVIDER: S-EPMC4027229 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Anthraquinone Derivatives as Potent Inhibitors of c-Met Kinase and the Extracellular Signaling Pathway.

Liang Zhongjie Z   Ai Jing J   Ding Xiao X   Peng Xia X   Zhang Dengyou D   Zhang Ruihan R   Wang Ying Y   Liu Fang F   Zheng Mingyue M   Jiang Hualiang H   Liu Hong H   Geng Meiyu M   Luo Cheng C  

ACS medicinal chemistry letters 20130225 4

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 hepatoc  ...[more]

Similar Datasets

Unknown Correction to Anthraquinone Derivatives as Potent Inhibitors of c-Met Kinase and the Extracellular Signaling Pathway.
| S-EPMC4329593 | biostudies-literature
Unknown MET-GRB2 Signaling-Associated Complexes Correlate with Oncogenic MET Signaling and Sensitivity to MET Kinase Inhibitors.
| S-EPMC5833309 | biostudies-literature
Unknown Novel 2-Carbonylbenzo[b]thiophene 1,1-Dioxide Derivatives as Potent Inhibitors of STAT3 Signaling Pathway.
| S-EPMC4569881 | biostudies-literature
Unknown Towards dual inhibitors of the MET kinase and WNT signaling pathway; design, synthesis and biological evaluation.
| S-EPMC9075752 | biostudies-literature
Unknown Potent and Selective CK2 Kinase Inhibitors with Effects on Wnt Pathway Signaling in Vivo.
| S-EPMC4789659 | biostudies-literature
Unknown Discovery of novel antitumor dibenzocyclooctatetraene derivatives and related biphenyls as potent inhibitors of NF-?B signaling pathway.
| S-EPMC3899348 | biostudies-literature
Unknown Bis-aryl urea derivatives as potent and selective LIM kinase (Limk) inhibitors.
| S-EPMC4349585 | biostudies-literature
Unknown Identification of novel piperazinylquinoxaline derivatives as potent phosphoinositide 3-kinase (PI3K) inhibitors.
| S-EPMC3419191 | biostudies-literature
Unknown Design, Synthesis, and Biological Evaluation of Novel Imidazo[1,2-a]pyridine Derivatives as Potent c-Met Inhibitors.
| S-EPMC4434476 | biostudies-literature
Unknown Discovery of novel quinazoline derivatives bearing semicarbazone moiety as potent EGFR kinase inhibitors.
| S-EPMC6232652 | biostudies-literature