摘要
原肌球蛋白受体激酶(TRK)是蛋白酪氨酸激酶家族的一员,其可对哺乳动物神经系统突触的可塑性进行调节,并在多种肿瘤中表达。对于TRK生理作用的研究相对完全,现有多个TRK抑制剂处于临床研究阶段,其中部分药物(如larotrectinib、entrectinib)已获FDA批准上市,表明TRK抑制剂具有较好的开发前景。本文作者介绍了TRK和NTRK融合蛋白的生物学功能,并对不同类型的TRK小分子抑制剂的开发过程、活性、选择性以及耐药性进行了综述。
Tropomyosin receptor kinase(TRK),a member of the protein tyrosine kinase family,regulates the synaptic plasticity of the mammalian nervous system,and is expressed in a variety of tumors.TRK has clear physiological activity.At the same time,many TRK inhibitors are in the clinical research stage,and some drugs(such as larotrectinib and entrectinib)have been approved by FDA,which shows that TRK inhibitors have good development prospects.This review focuses on summarizing the biological functions of TRK and NTRK fusion proteins,the development of small-molecule TRK inhibitors with different chemotypes,activity,selectivity and drug resistance.
作者
孙逸祥
吴天啸
秦桥花
刘念
赵冬梅
SUN Yi-xiang;WU Tian-xiao;QIN Qiao-hua;LIU Nian;ZHAO Dong-mei(Key Laboratory of Structure-Based Drug Design and Discovery(Shenyang Pharmaceutical University),Ministry of Education,Shenyang 110016,China)
出处
《中国药物化学杂志》
CAS
CSCD
2021年第6期470-483,共14页
Chinese Journal of Medicinal Chemistry
