具有烷基化功能基团的EGFR酪氨酸激酶抑制剂研究进展

Progress in Inhibitors of Epidermal Growth Factor Receptor with Alkylation Properties

近年来,针对肿瘤生长的关键调控因子,尤其是针对肿瘤信号通路中起关键调控作用的表皮生长因子受体酪氨酸激酶进行的小分子激酶抑制剂的研发为人们提供了有效对抗肿瘤的新策略。综述了以4-芳氨基喹唑啉为母核具有烷基化功能基的表皮生长因子受体酪氨酸激酶抑制剂的研究进展,介绍了产生烷基化作用的功能基团以及抑制剂对受体蛋白的作用机理和结合方式。

The tyrosine klnase epidermal growth factor receptor （EGFR） has emerged in recent years as a key regulatory factor and validated target of targeted therapies for solid tumors. It plays a central role in oncology including activation of signaling pathways that regulate proliferation ; angiogenesis decreased apoptosis, and loss of differentiation. This work reviews the recent progress in inhibitors of epidermal growth factor receptor with alkylation properties. The alkylation groups and inhibiting mechanism are introduced, with an em- phasis on the mechanism and binding manner of both irreversible EGFR kinase inhibitors and EGFR kinase inhibitors with DNA alkylation properties.