OBJECTIVE To discover a small molecule targeting ULK1-modulated cell death of triple negative breast cancer and exploreits potential mechanisms. METHODS ULK1 expression was analyzed by The Cancer Genome Atlas (TCGA) analysis and tissue microarray (TMA) analysis. ULK1 agonist was designed by using in silico screening, as well as modified by chemical synthesis and screened by kinase and anti-proliferative activities. The amino acid residues that key to the activation site of LYN-1604 were determined by site-directed mutagenesis, as well as in vitro kinase assay and ADP-Glo kinase assay. The mechanisms of LYN-1604 induced cell death were investigated by fluores?cence microscope, western blotting, flow cytometry analysis, immunocytochemistry, as well as siRNA and GFP-mRFP-LC3 plasmid transfections. Potential ULK1 interactors were discovered by performing comparative microarray analysis and the therapeutic effect of LYN-1604 was assessed by xenograft breast cancer mouse model. RESULTS We found that ULK1 was

来源：中国药理学与毒理学杂志 2017 年 31卷 10期