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RETRACTED ARTICLE

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Cancer Lett. 2017 Mar 28;389:41-48. doi: 10.1016/j.canlet.2016.12.030. Epub 2016 Dec 30.

SRI36160 is a specific inhibitor of Wnt/β-catenin signaling in human pancreatic and colorectal cancer cells.

Author information

1
Drug Discovery Division, Southern Research, 2000 Ninth Avenue South, Birmingham, AL 35255, USA. Electronic address: yli@southernresearch.org.
2
Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, USA.
3
Drug Discovery Division, Southern Research, 2000 Ninth Avenue South, Birmingham, AL 35255, USA.

Abstract

Activation of Wnt/β-catenin signaling is associated with pancreatic and colorectal cancer, among others. To-date, there are no FDA-approved small molecule Wnt/β-catenin inhibitors and many past efforts resulted in compounds with undesirable off-target effects. We recently identified a series of benzimidazole analogs as potent inhibitors of Wnt/β-catenin signaling. Here, we show that the lead compound SRI36160 displayed selective Wnt inhibition and potent antiproliferative activity in pancreatic and colorectal cancer cells. Moreover, SRI36160 had no effect on STAT3 and mTORC1 signaling in pancreatic and colorectal cancer cells, and was not effective in inhibiting proliferation of non-cancerous cells. Our findings suggest that this series of benzimidazole analogs presents a novel approach for the treatment of Wnt-dependent cancers such as colorectal and pancreatic cancer.

KEYWORDS:

Benzimidazole; Drug discovery; Niclosamide; Targeted therapy; Wnt signaling

PMID:
28043913
PMCID:
PMC5544029
DOI:
10.1016/j.canlet.2016.12.030
[Indexed for MEDLINE]
Free PMC Article

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