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

Bioorg Med Chem Lett. 2012 May 15;22(10):3571-4. doi: 10.1016/j.bmcl.2012.01.035. Epub 2012 Jan 25.

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).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Hydrazones / pharmacology*
  • Neoplastic Stem Cells / cytology*
  • Pyrroles / pharmacology*

Substances

  • Hydrazones
  • ML239
  • Pyrroles