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


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
StateAccepted/In press - Jan 1 2019


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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