ML239 (CID-49843203) is a potent and selective inhibitor of breast cancer stem cells, with an IC50 of 1.16 μM.

Breast cancer stem cells:1.16 μM.

ML239 (Compound 7j) serves as a powerful and selective inhibitor targeting breast cancer stem cells, exhibiting an IC50 value of 1.16 μM and demonstrating approximately 24-fold greater selectivity compared to the control cell line. It operates primarily by potentially activating fatty acid desaturase 2 (FADS2), thereby inhibiting the growth of breast cancer stem-like cells. Additionally, ML239 shows cytotoxic effects on NCIH661 cells. Interestingly, the reduction of FADS2 activity, either through direct knockdown or by using the FADS2 inhibitor SC-26196, diminishes the cytotoxicity of ML239 in cancer cell lines (CCLs), suggesting a critical role of FADS2 in ML239's mechanism of action.

ML239 is dissolved in DMSO.Cancer cell lines (CCLs) are plated at a density of 500 cells/well in white opaque tissue-culture-treated Aurora 1536-well MaKO plates in the provider-recommended growth media using a highly automated platform. Compounds (ML239) are added by acoustic transfer using a Labcyte Echo 555. 24 hours after plating. The effects of small molecules (ML239) are measured over a 16-point concentration range (two-fold dilution) in duplicate. DMSO is used at a constant concentration of 0.33%, including vehicle-only control wells. As a surrogate for viability, cellular ATP levels are assessed 72 hours after compound transfer by addition of CellTiterGlo followed by luminescence measurement using a ViewLux Microplate Imager. Duplicates are averaged and luminescence values normalized to vehicle (DMSO) treatment and background (media-only) wells