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

Fuchun Xie, Qiuhua Fan, Bingbing X. Li, Xiangshu Xiao

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalJournal of Medicinal Chemistry
DOIs
StateAccepted/In press - Jan 1 2019

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Cyclic AMP Response Element-Binding Protein
Genes
Prodrugs
Solubility
Neoplasms
Esters
Transcription Factors

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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abstract = "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.",
author = "Fuchun Xie and Qiuhua Fan and Li, {Bingbing X.} and Xiangshu Xiao",
year = "2019",
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doi = "10.1021/acs.jmedchem.9b01207",
language = "English (US)",
journal = "Journal of Medicinal Chemistry",
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AU - Xiao, Xiangshu

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AB - 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.

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