Leifu Yang, Yaxin Li, Yunling Du, Yan Guo, Zhenke Guo, Baoxiu Liu, Jianglin Liu, Yanfei Liu, Hongdan Niu, Yueming Sun, Henglin Yan, Yajuan Yang, Shannan Yu, Yifan Zhang, Yuan Zhang, Kun Zheng, Nanqiao Zheng, Xiaoqing Zhang, Qiang Zhang, Liming Hu
HER2 mutations were seen in 4% of non-small-cell lung cancer (NSCLC) patients. Most of these mutations (90%) occur as an insertion mutation within the exon 20 frame, leading to the downstream activation of the PI3K-AKT and RAS/MAPK pathways. However, no targeted therapies have yet been approved worldwide. Here a novel series of highly potent HER2 inhibitors with a pyrido[2,3,4- de ]quinazoline core were designed and developed. The derivatives with the pyrido[2,3,4- de ]quinazoline core displayed superior efficacy of antiproliferation in BaF3 cells harboring HER2insYVMA mutation compared with afatinib and neratinib...
March 22, 2024: Journal of Medicinal Chemistry