ML239 is the best-in-class inhibitor of the breast cancer stem cells with an IC50 = 1.16 µM. [1]
ML239 was a selective inhibitor an IC50= 1.18 µM against HMLE_sh_ECad, demonstrated a >23-fold selectivity over the control line, and was toxic to another CSC-like line, HMLE_shTwist, and a breast carcinoma cell line, MDA-MB-231. Five genes (ATP6V0C, PKM2, PPDPF, RPL23, and SERINC2) were differentially regulated in HMLE_sh_GFP after treatment with ML239. Gene expression studies conducted with ML239-treated cells showed altered gene expression in the NF-κB pathway in the HMLE_sh_ECad line but not in the isogenic control line. ML239 was selectively toxic toward another CSC-like cell line, HMLE_Twist, and the breast cancer line, MDA-MB-231. Similar to the results observed in the HMLE_sh_ECad cell line, ML239 was potently toxic, inhibiting HMLE_Twist with an IC50 ~0.1 µM. ML239 displayed potent toxicity (IC50 = 2.81 µM) to the breast carcinoma cell line, MDA-MB-231 [1]. ML239 also alters the expression of genes in the NF-κB, MAPK and inflammatory cytokine pathways.
Reference:
1.Phenotypic high-throughput screening elucidates target pathway in breast cancer stem cell-like cells. J Biomol Screen. 2012 Oct;17(9):1204-10. Epub 2012 Aug 30.