Identification of a selective small molecule inhibitor of breast cancer stem cells

Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Bioorganic & medicinal chemistry letters (Impact Factor: 2.65). 01/2012; 22(10):3571-4. DOI: 10.1016/j.bmcl.2012.01.035
Source: PubMed

ABSTRACT A high-throughput screen (HTS) with the National Institute of Health-Molecular Libraries Small Molecule Repository (NIH-MLSMR) compound collection identified a class of acyl hydrazones to be selectively lethal to breast cancer stem cell (CSC) enriched populations. Medicinal chemistry efforts were undertaken to optimize potency and selectivity of this class of compounds. The optimized compound was declared as a probe (ML239) with the NIH Molecular Libraries Program and displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control line (HMLE_sh_GFP).

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