PUBLICATION
IMU1003, an atrarate derivative, inhibits Wnt/β-catenin signaling
- Authors
- Yonezawa, H., Sugawara, A., Sakyo, T., Uehara, Y., Kawano, T., Nishiya, N.
- ID
- ZDB-PUB-200908-2
- Date
- 2020
- Source
- Biochemical and Biophysical Research Communications 532(3): 440-445 (Journal)
- Registered Authors
- Nishiya, Naoyuki
- Keywords
- Atrarate, Inhibitor, Wnt, Zebrafish, β-catenin
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Antineoplastic Agents/pharmacology
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Cell Survival/drug effects
- Down-Regulation/drug effects
- Drug Screening Assays, Antitumor
- Gene Expression/drug effects
- HEK293 Cells
- Humans
- Hydroxybenzoates/pharmacology*
- Mutation
- Wnt Signaling Pathway/drug effects*
- Wnt Signaling Pathway/genetics
- Zebrafish/embryology
- Zebrafish/genetics
- beta Catenin/metabolism*
- PubMed
- 32891433 Full text @ Biochem. Biophys. Res. Commun.
Citation
Yonezawa, H., Sugawara, A., Sakyo, T., Uehara, Y., Kawano, T., Nishiya, N. (2020) IMU1003, an atrarate derivative, inhibits Wnt/β-catenin signaling. Biochemical and Biophysical Research Communications. 532(3):440-445.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping