화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.532, No.3, 440-445, 2020
IMU1003, an atrarate derivative, inhibits Wnt/beta-catenin signaling
Aberrant activation of the canonical Wnt/beta-catenin signaling pathway triggers tumorigenesis in various tissues. This study identified an atrarate compound, IMU14, derived from filamentous fungi as an inhibitor of Wnt/beta-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 beta-catenin/TCF-dependent transcriptional activation and decreased nuclear beta-catenin level. In addition, IMU1003 selectively decreased viability and target gene products of the Wnt/beta-catenin signaling pathway in human non-colorectal cancer cell lines harboring intact APC and beta-catenin. Therefore, atrarate derivatives inhibit Wnt/beta-catenin signaling and show anticancer potential, and we developed a new class of chemical backbones for Wnt/beta-catenin signaling inhibitors. (C) 2020 Elsevier Inc. All rights reserved.