Cinnamides as selective small-molecule inhibitors of a cellular model of breast cancer stem cells

  • Bioorg Med Chem Lett. 2013 Mar 15;23(6):1834-8. doi: 10.1016/j.bmcl.2013.01.025.
Andrew R Germain  1 ,  Leigh C Carmody ,  Partha P Nag ,  Barbara Morgan ,  Lynn Verplank ,  Cristina Fernandez ,  Etienne Donckele ,  Yuxiong Feng ,  Jose R Perez ,  Sivaraman Dandapani ,  Michelle Palmer ,  Eric S Lander ,  Piyush B Gupta ,  Stuart L Schreiber ,  Benito Munoz
Affiliations
  • 1. Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
PMID: 23403082 DOI: 10.1016/j.bmcl.2013.01.025
Abstract

A high-throughput screen (HTS) was conducted against stably propagated Cancer stem cell (CSC)-enriched populations using a library of 300,718 compounds from the National Institutes of Health (NIH) Molecular Libraries Small Molecule Repository (MLSMR). A cinnamide analog displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control cell line (HMLE_sh_eGFP). Herein, we report structure-activity relationships of this class of cinnamides for selective lethality towards CSC-enriched populations.