Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Bioorg Med Chem Lett. 2012 May 15;22(10):3571-4. doi: 10.1016/j.bmcl.2012.01.035. Epub 2012 Jan 25.
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).
高通量筛选（HTS）结合美国国立卫生研究院-分子图书馆小分子库（NIH-MLSMR）化合物库，鉴定出一类酰腙类化合物，对富集乳腺癌干细胞（CSC）的群体具有选择性杀伤作用。药物化学研究旨在优化这一类化合物的活性和选择性。经优化的化合物被美国国立卫生研究院分子图书馆计划宣布为探针（ML239），对乳腺癌类干细胞样细胞系（HMLE_sh_Ecad）的选择性抑制作用大于 20 倍，而对同基因对照系（HMLE_sh_GFP）则没有抑制作用。
