第4代小分子表皮生长因子受体-酪氨酸激酶抑制剂研究进展  

Research Progress of the Fourth Generation of Small Molecule Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors

作　　者：邓连力 DENG Lianli(The People's Hospital of Xiushan Tujia and Miao Autonomous County,Chongqing,China 409900)

机构地区：[1]重庆市秀山土家族苗族自治县人民医院,重庆409900

出　　处：《中国药业》2023年第15期127-128,I0001-I0004,共6页China Pharmaceuticals

摘　　要：目的总结抗肿瘤药物第4代小分子表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKIs)的研究与应用进展。方法计算机检索PubMed,SCI-hub,CNKI数据库自建库起至2022年9月第4代小分子EGFR-TKIs的相关研究文献,分析各抑制剂的抗肿瘤活性、作用位点及研究情况。结果已开展临床研究的第4代小分子EGFR-TKIs包括ES-072,TQB3804,BLU-945,其中ES-072和BLU-945治疗非小细胞肺癌安全、有效,且不良反应较轻;开展临床前研究的第4代小分子EGFR-TKIs包括EAI045,JBJ-04-125-02,BI-4020,JND3229,CH7233163,AZ7608。除ES-072外,其余抑制剂的半数抑制浓度均为纳摩尔级;作用机制为T790M,C797S,L858R,19Del等位点的二重或三重突变。结论各抑制剂的作用位点明确,但应进一步加强临床研究。Objective To summarize the research and application progress of the fourth generation small molecule epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs).Methods By searching the relevant literature on the fourth generation of small molecule EGFR-TKIs in the PubMed,SCI-hub,and CNKI databases from the inception to September 2022,and the anti-tumor activity,action sites and research progress of these inhibitors were summarized.Results The fourth generation of small molecule EGFR-TKIs that have been clinically studied include ES-072,TQB3804,and BLU-945.Among them,ES-072 and BLU-945 are safe,effective,and have mild adverse drug reactions in the treatment of non-small cell lung cancer(NSCLC).The fourth generation of small molecule EGFR-TKIs in preclinical studies include EAI045,JBJ-04-125-02,BI-4020,JND3229,CH7233163,and AZ7608.Except for ES-072,the half inhibitory concentration of all other inhibitors is at the nanomolar level.The mechanism is a double or triple mutation at T790M,C797S,L858R,19Del and other loci.Conclusion The action sites of each inhibitor are clear,but further clinical research should be strengthened.

关 键 词：抗肿瘤药物 第4代小分子表皮生长因子受体-酪氨酸激酶抑制剂 作用位点 抗肿瘤活性 

分 类 号：R979.1[医药卫生—药品]