Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amentoflavone has been identified as a JAK2 inhibitor by structure-based virtual screening of a natural product library. In silico optimization using the DOLPHIN model yielded analogues with enhanced potency against JAK2 activity and HCV activity in cellulo. Molecular modeling and kinetic experiments suggested that the analogues may function as Type II inhibitors of JAK2.
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PMID:Virtual screening and optimization of Type II inhibitors of JAK2 from a natural product library. 2542 23

Hepatocellular carcinoma (HCC) has become a burden on public health worldwide. Therefore, development of novel therapeutic agents for managing HCC is imperative. Amentoflavone (AF), a flavonoid compound extracted from Selaginella tamariscina Spring, reportedly has anti-neoplastic activities. The aim of this study was to investigate the role of AF in HCC and the underlying mechanism of action. We found that AF decreased cell viability in a dose-dependent manner in both HCC cell lines but did not affect the viability of a normal hepatic cell line. The anti-growth effect of AF against HCC was also confirmed in the xenograft model. Standard histological examination of the xenograft tissues also revealed minimal in vivo toxicity of AF. The In vitro and in vivo models also provided evidence of the pro-apoptotic activity of AF. In addition, AF significantly inhibited glycolysis via HK2 repression; further dissection of the underlying mechanism revealed that AF downregulated HK2 by generating ROS and hence inhibiting the JAK2/STAT3 signaling pathway. In conclusion, AF induced apoptosis and inhibited glycolysis in HCC by targeting HK2. Our findings provide preliminary experimental data that support further investigation of the therapeutic efficacy of AF in HCC.
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PMID:Amentoflavone suppresses hepatocellular carcinoma by repressing hexokinase 2 expression through inhibiting JAK2/STAT3 signaling. 3284 35