IMU1003, an atrarate derivative, inhibits Wnt/β-catenin signaling

被引：5

作者：

Yonezawa, Honami ^{[1
]}

Sugawara, Aoi ^{[2
]}

Sakyo, Tomoko ^{[1
]}

Uehara, Yoshimasa ^{[1
]}

Kawano, Tomikazu ^{[2
]}

Nishiya, Naoyuki ^{[1
]}

机构：

[1] Iwate Med Univ, Dept Clin Pharm, Div Integrated Informat Pharmaceut Sci, Sch Pharm, 1-1-1 Idaidori, Yahaba, Iwate 0283694, Japan

[2] Iwate Med Univ, Dept Pharmaceut Sci, Div Med & Organ Chem, Sch Pharm, 1-1-1 Idaidori, Yahaba, Iwate 0283694, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2020年 / 532卷 / 03期

关键词：

Zebrafish; Wnt; beta-catenin; Atrarate; Inhibitor; BETA-CATENIN; ANDROGEN RECEPTOR; CANCER; MUTATIONS; EXPRESSION; ANTAGONIST; ACTIVATION; COMPLEX; TARGET; ACID;

D O I：

10.1016/j.bbrc.2020.08.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：440 / 445

页数：6

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