ICG-001, A Novel Small Molecule Regulator of TCF/β-Catenin Transcription

被引：98

作者：

Eguchi, Masakatsu ^{[1
]}

Cu Nguyen ^{[1
]}

Lee, Sung Chan ^{[1
]}

Kahn, Michael ^{[1
,2
]}

机构：

[1] Inst Chem Genom, Seattle, WA 98122 USA

[2] Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA

来源：

MEDICINAL CHEMISTRY | 2005年 / 1卷 / 05期

关键词：

Peptidomimetics; Anti-cancer; Wnt Pathway; beta-Catenin;

D O I：

10.2174/1573406054864098

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Inherited and somatic mutations in the APC gene, a human tumor-suppressor, occur in a large percentage of colon cancers, leading to elevated levels of nuclear beta-Catenin, and to activation of TCF/beta-Catenin-responsive genes including cyclin D1 and c-myc. To identify small molecule antagonists of this pathway, we screened transformed colorectal cells with a secondary structure-templated chemical library, in search of compounds that attenuated a TCF/beta-Catenin-responsive reporter gene. From this library we selected ICG-001 (IC50 = 3 mu M) as a lead compound. Design and synthesis of the chemical library and some preliminary biological evaluation is described.

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收藏

页码：467 / 472

页数：6

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