Research Papers:

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

Yonghe Li _, Wenyan Lu, Surendra K. Saini, Omar Moukha-Chafiq, Vibha Pathak and Subramaniam Ananthan

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Oncotarget. 2016; 7:11263-11270. https://doi.org/10.18632/oncotarget.7019

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Yonghe Li1, Wenyan Lu1, Surendra K. Saini1, Omar Moukha-Chafiq1, Vibha Pathak1, Subramaniam Ananthan1

1Drug Discovery Division, Southern Research Institute, Birmingham, AL 35205, United States of America

Correspondence to:

Yonghe Li, e-mail: yli@southernresearch.org

Subramaniam Ananthan, e-mail: sananthan@southernresearch.org

Keywords: Wnt signaling, Wnt inhibitor, quinazoline, colorectal cancer, drug discovery

Received: July 29, 2015     Accepted: January 13, 2016     Published: January 25, 2016


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.

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