Identification of quinazoline compounds as novel potent inhibitors of Wnt/β-catenin signaling in colorectal cancer cells

Oncotarget. 2016 Mar 8;7(10):11263-70. doi: 10.18632/oncotarget.7019.


The Wnt/β-catenin signaling pathway is critical for the initiation and progression of most colon cancers, and has emerged as one of the most promising targets for colorectal cancer chemoprevention and treatment. In this study, we have discovered a structurally related series of quinazolines as potent inhibitors of Wnt/β-catenin signaling in colorectal cancer cells harboring mutations in CTNNB1 or APC. We showed that the quinazoline leads suppressed Wnt/β-catenin signaling without altering the level of β-catenin protein in colorectal cancer cells, suggesting that they act on the downstream elements of the pathway. Moreover, the quinazoline leads displayed potent anticancer activities with IC50 values between 4.9 and 17.4 μM in colorectal cancer cells. Importantly, we also found that a structurally related quinazoline lacking inhibitory effect on Wnt/β-catenin signaling was unable to suppress colorectal cancer cell proliferation. Together, these results suggest that the quinazoline lead compounds identified in this study have therapeutic potential for the prevention and treatment of colorectal cancer.

Keywords: Wnt inhibitor; Wnt signaling; colorectal cancer; drug discovery; quinazoline.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / metabolism*
  • Drug Screening Assays, Antitumor
  • Humans
  • Inhibitory Concentration 50
  • Quinazolines / pharmacology*
  • Wnt Signaling Pathway / drug effects*


  • Antineoplastic Agents
  • Quinazolines