School of Pharmacy, Weifang Medical University, Weifang, Shandong, China.
School of Basic Medicine, Weifang Medical University, Weifang, Shandong, China.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2205605. doi: 10.1080/14756366.2023.2205605.
EGFR mutations have been identified in 20,000 reported NSCLC (non-small cell lung cancer) samples, and exon 19 deletions and L858R mutations at position 21, known as "classical" mutations, account for 85-90% of the total EGFR (epidermal growth factor receptor) mutations. In this paper, two series of EGFR kinase inhibitors were designed and synthesised. Among them, compound showed an IC value of 13 nM for kinase inhibitory activity against EGFR and more than 76-fold selectivity for EGFR. Furthermore, in an in vitro anti-tumour activity test, compound showed an effective anti-proliferation activity against H1975 cells with an IC value of 0.087 μΜ. We also verified the mechanism of action of compound as a selective inhibitor of EGFR by cell migration assay and apoptosis assay.
在已报道的 20000 例 NSCLC（非小细胞肺癌）样本中，已发现 EGFR 突变，外显子 19 缺失和位于 21 位的 L858R 突变，被称为“经典”突变，占 EGFR（表皮生长因子受体）突变的 85-90%。在本文中，设计并合成了两个系列的 EGFR 激酶抑制剂。其中，化合物对 EGFR 的激酶抑制活性的 IC 值为 13 nM，对 EGFR 的选择性超过 76 倍。此外，在体外抗肿瘤活性测试中，化合物对 H1975 细胞的增殖抑制活性的 IC 值为 0.087 μΜ。我们还通过细胞迁移实验和细胞凋亡实验验证了化合物作为 EGFR 选择性抑制剂的作用机制。
