Small molecule screen for inhibitors of expression from canonical CREB response element-containing promoters

Bryan Mitton, Katie Hsu, Ritika Dutta, Bruce C. Tiu, Nick Cox, Kevin G. McLure, Hee Don Chae, Mark Smith, Elizabeth A. Eklund, David E. Solow-Cordero, Kathleen M. Sakamot*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The transcription factor CREB (cAMP Response Element Binding Protein) is an important determinant in the growth of Acute Myeloid Leukemia (AML) cells. CREB overexpression increases AML cell growth by driving the expression of key regulators of apoptosis and the cell cycle. Conversely, CREB knockdown inhibits proliferation and survival of AML cells but not normal hematopoietic cells. Thus, CREB represents a promising drug target for the treatment of AML, which carries a poor prognosis. In this study, we performed a high-throughput small molecule screen to identify compounds that disrupt CREB function in AML cells. We screened ~114,000 candidate compounds from Stanford University's small molecule library, and identified 5 molecules that inhibit CREB function at micromolar concentrations, but are non-toxic to normal hematopoietic cells. This study suggests that targeting CREB function using small molecules could provide alternative approaches to treat AML.

Original languageEnglish (US)
Pages (from-to)8653-8662
Number of pages10
JournalOncotarget
Volume7
Issue number8
DOIs
StatePublished - 2016

Keywords

  • CREB
  • Novel therapeutics
  • Small molecule screen

ASJC Scopus subject areas

  • Oncology

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