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Oncotarget. 2016 Feb 23;7(8):8653-62. doi: 10.18632/oncotarget.7085.

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

Author information

1
Department of Pediatrics, Stanford University, Stanford, CA, USA.
2
Medicinal Chemistry Knowledge Center, Stanford ChEM-H, Stanford, CA, USA.
3
Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
4
High-Throughput Bioscience Center, Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.

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.

KEYWORDS:

CREB; novel therapeutics; small molecule screen

PMID:
26840025
PMCID:
PMC4890994
DOI:
10.18632/oncotarget.7085
[Indexed for MEDLINE]
Free PMC Article

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