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Published on: October 27, 2014
IMU1003, an atrarate derivative, inhibits Wnt/β-catenin signaling
Honami Yonezawa1, Aoi Sugawara2, Tomoko Sakyo1
1Division of Integrated Information for Pharmaceutical Sciences, Department of Clinical Pharmacy, Iwate Medical University School of Pharmacy, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan.
Abstract:
Aberrant activation of the canonical Wnt/β-catenin signaling pathway triggers tumorigenesis in various tissues. This study identified an atrarate compound, IMU14, derived from filamentous fungi as an inhibitor of Wnt/β-catenin signaling in phenotypic chemical inhibitor screening of the zebrafish eyeless phenotype. Its derivatization resulted in synthesis of IMU1003 with enhanced Wnt inhibitory activity. IMU1003 inhibited β-catenin/TCF-dependent transcriptional activation and decreased nuclear β-catenin level. In addition, IMU1003 selectively decreased viability and target gene products of the Wnt/β-catenin signaling pathway in human non-colorectal cancer cell lines harboring intact APC and β-catenin. Therefore, atrarate derivatives inhibit Wnt/β-catenin signaling and show anticancer potential, and we developed a new class of chemical backbones for Wnt/β-catenin signaling inhibitors.
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