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

  • J Cell Biochem. 2015 Aug;116(8):1595-601. doi: 10.1002/jcb.25113.
Gina Chun Kost  1 ,  Mi Young Yang  1 ,  Liangwei Li  2 ,  Yinwei Zhang  2 ,  Chia-Yi Liu  2 ,  Deog Joong Kim  1 ,  Chang-Ho Ahn  1 ,  Young Bok Lee  1 ,  Zhi-Ren Liu  2
Affiliations
  • 1. Rexahn Pharmaceuticals, Inc., Rockville, Maryland, 20850.
  • 2. Department of Biology, Georgia State University, Atlanta, Georgia, 30303.
PMID: 25649741 DOI: 10.1002/jcb.25113
Abstract

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 20 nM. 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 (3) H-labeled RX-5902 to Y593 phospho-p68 RNA helicase. We further demonstrated RX-5902 inhibited the β-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 β-catenin pathway, such as c-Myc, cyclin D1 and p-c-Jun. Therefore, our study indicates that the inhibition of Y593 phospho-p68 helicase - β-catenin interaction by direct binding of RX-5902 to Y593 phospho-p68 RNA helicase may contribute to the anti-cancer activity of this compound.

Keywords
ANTI-CANCER; PHOSPHO-p68; RX-5902; p68 RNA HELICASE.
Products