title: Identification of a selective small molecule inhibitor of breast cancer stem cells.
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).
authors.affiliation: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Germain
authors.forename: Leigh C
authors.initials: LC
authors.lastname: Carmody
authors.forename: Barbara
authors.initials: B
authors.lastname: Morgan
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernandez
authors.forename: Erin
authors.initials: E
authors.lastname: Forbeck
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Lewis
authors.forename: Partha P
authors.initials: PP
authors.lastname: Nag
authors.forename: Amal
authors.initials: A
authors.lastname: Ting
authors.forename: Lynn
authors.initials: L
authors.lastname: VerPlank
authors.forename: Yuxiong
authors.initials: Y
authors.lastname: Feng
authors.forename: Jose R
authors.initials: JR
authors.lastname: Perez
authors.forename: Sivaraman
authors.initials: S
authors.lastname: Dandapani
authors.forename: Michelle
authors.initials: M
authors.lastname: Palmer
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Piyush B
authors.initials: PB
authors.lastname: Gupta
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Schreiber
authors.forename: Benito
authors.initials: B
authors.lastname: Munoz
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000166:cytology*; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: D006835:Hydrazones; C578078:ML239; D011758:Pyrroles