@article{APS10693,
author = {Jiang-yan Cao and Shuang Qi and Hong Wu and Ao-li Wang and Qing-wang Liu and Xi-xiang Li and Bei-lei Wang and Juan Ge and Feng-ming Zou and Cheng Chen and Jun-jie Wang and Chen Hu and Jing Liu and Wen-chao Wang and Qing-song Liu},
title = {CHMFL-26 is a highly potent irreversible HER2 inhibitor for use in the treatment of HER2-positive and HER2-mutant cancers},
journal = {Acta Pharmacologica Sinica},
volume = {43},
number = {10},
year = {2022},
keywords = {},
abstract = {Oncogene HER2 is amplified in 20%–25% of human breast cancers and 6.1%–23.0% of gastric cancers, and HER2-directed therapy significantly improves the outcome for patients with HER2-positive cancers. However, drug resistance is still a clinical challenge due to primary or acquired mutations and drug-induced negative regulatory feedback. In this study, we discovered a potent irreversible HER2 kinase inhibitor, CHMFL-26, which covalently targeted cysteine 805 of HER2 and effectively overcame the drug resistance caused by HER2 V777L, HER2 L755S, HER2 exon 20 insertions, and p95-HER2 truncation mutations. CHMFL-26 displayed potent antiproliferation efficacy against HER2-amplified and mutant cells through constant HER2-mediated signaling pathway inhibition and apoptosis induction. In addition, CHMFL-26 suppressed tumor growth in a dose-dependent manner in xenograft mouse models. Together, these results suggest that CHMFL-26 may be a potential novel anti-HER2 agent for overcoming drug resistance in HER2-positive cancer therapy.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10693}
}