ACS Comb Sci. 2020 Sep 22. doi: 10.1021/acscombsci.0c00027. Online ahead of print.
TRAF2 and NCK-interacting kinase (TNIK) is a critical factor in colorectal cancer (CRC) proliferation mediated by Wnt signaling. We attempted to identify efficient TNIK inhibitors using computational high throughput virtual screening (HTVS) from various drug banks and databases. By performing/ On performing e-pharmacophore screening and molecular docking methods, from ~700000 molecules, compounds LC_222150, LC_112060, and LC_64796 were identified as potential leads, through molecular dynamics (MD) simulations and density functional theory (DFT). These top 3 structures were commercially procured, and their inhibitory activity was assessed in vitro. Significant TNIK inhibition was observed, with an average IC50 of 18.33±0.75 nM. In terms of anti-cancer activity, the observed average relative % activity (RPA) of 90.28±1.04 for these compounds compared well with doxorubicin (86.75±1.45) as a standard. Compounds LC_222150, LC_112060, and LC_64796, therefore, warrant further evaluation in vivo to assess their CRC therapeutic effects.