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Identification of Small Molecule Hes1 Modulators as Potential Anticancer Chemotherapeutics
Author(s) -
Sail Vibhavari,
Hadden M. Kyle
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12059
Subject(s) - hes1 , downregulation and upregulation , notch signaling pathway , cancer research , small molecule , regulator , signal transduction , chemistry , cell culture , microbiology and biotechnology , biology , biochemistry , genetics , gene
Hes1 is a key transcriptional regulator primarily controlled by the Notch signaling pathway, and recent studies have demonstrated both an oncogenic and tumor suppressor role for Hes1, depending on the cell type. Small molecules that activate and inhibit Hes1 activity hold promise as future anticancer chemotherapeutics. We have utilized a cell‐based dual luciferase assay to identify modulators of Hes1 expression in a medium‐throughput format. A modest screen was performed in HCT‐116 colon cancer cell lines, and two small molecules were identified and characterized as Hes1 regulators. Compound 3 induced Hes1 expression and exhibited anticancer effects in pulmonary carcinoid tumor cells, a cell type in which the upregulated Notch/Hes1 signaling plays a tumor suppressive role. Treatment of HCT‐116 cells with compound 12 resulted in Hes1 downregulation and antitumor effects.