A Novel Anti-Cancer Agent, 1-(3,5-Dimethoxyphenyl)-4-[(6-Fluoro-2-Methoxyquinoxalin-3-yl)Aminocarbo nyl] Piperazine (RX-5902), Interferes With -Catenin Function Through Y593 Phospho-p68 RNA Helicase

作者：Kost Gina Chun; Yang Mi Young; Li Liangwei; Zhang Yinwei; Liu Chia Yi; Kim Deog Joong; Ahn Chang Ho; Lee Young Bok^*; Liu Zhi Ren

来源：Journal of Cellular Biochemistry, 2015, 116(8): 1595-1601.

DOI：10.1002/jcb.25113

• ANTI-CANCER
• p68 RNA HELICASE
• PHOSPHO-p68
• RX-5902

1-(3,5-Dimethoxyphenyl)-4-[(6-fluoro-2-methoxyquinoxalin-3-yl)aminocarbonyl] piperazine (RX-5902) exhibits strong growth inhibition in various human cancer cell lines with IC50 values ranging between 10 and 20nM. In this study, we demonstrate that p68 RNA helicase is a cellular target of RX-5902 by the drug affinity responsive target stability (DARTS) method, and confirmed the direct binding of H-3-labeled RX-5902 to Y593 phospho-p68 RNA helicase. We further demonstrated RX-5902 inhibited the -catenin dependent ATPase activity of p68 RNA helicase in an in vitro system. Furthermore, we showed that treatment of cancer cells with RX-5902 resulted in the downregulation of the expression of certain genes, which are known to be regulated by the -catenin pathway, such as c-Myc, cyclin D1 and p-c-Jun. Therefore, our study indicates that the inhibition of Y593 phospho-p68 helicase - -catenin interaction by direct binding of RX-5902 to Y593 phospho-p68 RNA helicase may contribute to the anti-cancer activity of this compound. J. Cell. Biochem. 116: 1595-1601, 2015.

• 出版日期2015-8