Kang Jia-Xiong, Li Chao, Cheng Yi-Mei, Huang Mou-Xin, Zhao Guang-Kuan, Jin Zhi-Liang, Qi Xiao-Wei, Gu Jing, Ouyang Qin
Department of Medicinal Chemistry, Third Military Medical University, Chongqing, 400038, China.
Department of Pharmacy, Sichuan Hospital of PAP, Leshan, 614000, China.
Curr Med Chem. 2024 Jun 10. doi: 10.2174/0109298673308896240528173317.
As members of the protein tyrosine kinase family, the Epidermal Growth Factor Receptor (EGFR) and Human Epidermal Growth Factor Receptor 2 (HER2) play essential roles in cellular signal transduction pathways. Overexpression or abnormal activation of EGFR and HER2 can lead to the development of various solid tumors. Therefore, they have been confirmed as biological targets for the development of anticancer drugs. Due to the fact that many cancers are highly susceptible to developing resistance to single-target EGFR inhibitors in clinical practice, dual inhibitors that target both EGFR and HER2 have been developed to increase efficacy, reduce drug resistance and interactions, and improve patient compliance. Currently, a variety of EGFR/HER2 dual inhibitors have been developed, with several drugs already approved for marketing or in clinical trials. In this review, we summarize recent advancements in small-molecule EGFR/HER2 dual inhibitors by focusing on structure-activity relationships and share novel insights into developing anticancer agents.
作为蛋白质酪氨酸激酶家族的成员，表皮生长因子受体（EGFR）和人表皮生长因子受体2（HER2）在细胞信号转导通路中发挥着重要作用。EGFR和HER2的过表达或异常激活可导致各种实体瘤的发生。因此，它们已被确认为抗癌药物开发的生物学靶点。由于在临床实践中许多癌症对单靶点EGFR抑制剂极易产生耐药性，因此已开发出同时靶向EGFR和HER2的双靶点抑制剂，以提高疗效、降低耐药性和药物相互作用，并提高患者的依从性。目前，已开发出多种EGFR/HER2双靶点抑制剂，有几种药物已获批准上市或正在进行临床试验。在本综述中，我们通过聚焦构效关系总结小分子EGFR/HER2双靶点抑制剂的最新进展，并分享开发抗癌药物的新见解。
