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1. Discovery of SPH5030, a Selective, Potent, and Irreversible Tyrosine Kinase Inhibitor for HER2-Amplified and HER2-Mutant Cancer Treatment

Author

Di Li, Yuanxiang Tu, Kaijun Jin, Lingjun Duan, Yuan Hong, Jia Xu, Na Chen, Zhihui Zhang, Hongjian Zuo, Wanchun Gong, Jing Zhang, Qian Wang, Hai Qian, Xuenan Wang, Ying Ke, and Guangxin Xia

Subjects
Mice, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols, Drug Discovery, Animals, Humans, Molecular Medicine, Breast Neoplasms, Female, Protein Kinase Inhibitors
Abstract

Small-molecule irreversible tyrosine kinase inhibitors as high potent agents have led to improvements in disease-free and overall survival in patients with HER2-amplified cancer. The approved irreversible HER2 inhibitors, neratinib and pyrotinib, both lack HER2 selectivity, leading to off-target adverse events in patients. The development of HER2 mutation during treatment also hampers the progress of the treatment. We used a molecular hybridization strategy for structural optimizations, in conjunction with

Published
2022

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