原肌球蛋白受体激酶小分子抑制剂研究进展  

Advances in Research on Small Molecule Inhibitors of Tropomyosin Receptor Kinase

作　　者：杨雪晴 代金连 吴呈龙 刘宗亮[1] YANG Xueqing;DAI Jinlian;WU Chenglong;LIU Zongliang(Key Laboratory of Molecular Pharmacology and Drug Evaluation,Yantai University,Yantai 264005,China)

机构地区：[1]烟台大学分子药理学与药物评价教育部重点实验室,山东烟台264005

出　　处：《药学进展》2023年第3期194-206,共13页Progress in Pharmaceutical Sciences

摘　　要：原肌球蛋白受体激酶(TRK)属于酪氨酸激酶家族,由神经营养酪氨酸受体激酶(NTRK)基因编码,参与神经元的分化。NTRK基因与其他基因发生融合则与癌症的发病机制密切相关。近年来靶向作用于TRK的小分子抑制剂成为治疗癌症的一种新策略,现有多个TRK抑制剂处于不同的临床研究阶段,拉罗替尼和恩曲替尼分别于2018和2019年获FDA批准上市。介绍了TRK的结构及代表性TRK抑制剂研究进展,并对TRK抑制剂研发的未来前景以及克服耐药性的治疗策略进行了展望。Tropomyosin receptor kinase(TRK)belongs to the tyrosine kinases family.It is encoded by the gene of neurotrophic tyrosine receptor kinase(NTRK)and partcipates in the diferentiation of neurons.The fusion of NTRK with other genes is closely related to the pathogenesis of cancer.In recent years,small molecule inhibitors targeting TRK have become a new strategy for cancer treatment.Several TRK inhibitors are currently in different clinical research stages.Larotrectinib and entrectinib have been approved by FDA in 2018 and 2019,respectively.In this article,the structure of TRK and research progress of some representative TRK inhibitors have been introduced,and the future of TRK inhibitors R&D and treatment strategies to overcome drug resistance have been prospected.

关 键 词：原肌球蛋白受体激酶 抑制剂 抗肿瘤 耐药性 

分 类 号：R914.2[医药卫生—药物化学]