Discovery of a Synergistic Inhibitor of cAMP-Response Element Binding Protein (CREB)-Mediated Gene Transcription with 666-15

被引：13

作者：

Xie, Fuchun ^{[1
]}

Fan, Qiuhua ^{[1
]}

Li, Bingbing X. ^{[1
]}

Xiao, Xiangshu ^{[1
,2
]}

机构：

[1] Oregon Hlth & Sci Univ, Dept Chem Physiol & Biochem, Program Chem Biol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA

[2] Oregon Hlth & Sci Univ, Knight Canc Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2019年 / 62卷 / 24期

关键词：

CREB; PROMOTES; DESIGN;

D O I：

10.1021/acs.jmedchem.9b01207

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

CREB is a transcription factor implicated in the pathogenesis of multiple cancers. Targeting CREB is a promising strategy to develop potential cancer therapeutics. Previously, we identified 666-15 as a potent CREB inhibitor. Herein, we designed an ester prodrug of 666-15 through a long-range O,N-acyl transfer reaction for improved aqueous solubility. Unexpectedly, we discovered a small molecule 11 (653-47) that can potentiate the CREB inhibitory activity of 666-15 although 653-47 alone does not inhibit CREB.

引用

收藏

页码：11423 / 11429

页数：7

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