| RRC ID |
64803
|
| 著者 |
Yonezawa H, Sugawara A, Sakyo T, Uehara Y, Kawano T, Nishiya N.
|
| タイトル |
IMU1003, an atrarate derivative, inhibits Wnt/β-catenin signaling.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| 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.
|
| 巻・号 |
532(3)
|
| ページ |
440-445
|
| 公開日 |
2020-11-12
|
| DOI |
10.1016/j.bbrc.2020.08.031
|
| PII |
S0006-291X(20)31588-6
|
| PMID |
32891433
|
| MeSH |
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*
|
| IF |
2.985
|
| リソース情報 |
| ゼブラフィッシュ |
RIKEN WT |
