原肌球蛋白受体激酶抑制剂临床研究进展  

Advances in Clinical Research on Tropomyosin Receptor Kinase Inhibitors

作　　者：刘淼 刘晓 韩开红 韩开林[4] LIU Miao;LIU Xiao;HAN Kaihong;HAN Kailin(Department of Internal Medicine,Jining Psychiatric Hospital,Jining 272000,China;The Central Pharmaceutical Co.,Ltd.Tianjin 300400,China;Psychiatric Department,Jining Psychiatric Hospital,Jining 272000,China;Tasly R&D Institute,Tasly Holding Group Co.,Ltd,Tianjin 300410,China)

机构地区：[1]济宁市精神病防治院内科,山东济宁272000 [2]天津市中央药业有限公司,天津300400 [3]济宁市精神病防治院精神科,山东济宁272000 [4]天士力控股集团有限公司研究院,天津300410

出　　处：《药学进展》2022年第5期388-400,共13页Progress in Pharmaceutical Sciences

摘　　要：原肌球蛋白受体激酶(TRK)家族由神经受体酪氨酸激酶基因(NTRK)编码,并在神经系统的发育和正常功能中起重要作用。NTRK融合基因是各种成人和儿童癌症的致癌驱动因子。因此,近几年来TRK抑制剂被广泛关注和深入研究,首代TRK抑制剂拉罗替尼和恩曲替尼的成功获批具有里程碑式的意义。与其他激酶抑制剂相似,患者随着接受TRK抑制剂治疗时间的推移而产生耐药性,因此,解决耐药和多种突变将是未来研发的重点。通过对近几年具有不同结构类型、活性及选择性的小分子TRK抑制剂的研发进展进行详细总结,以期为进一步开发新型TRK抑制剂提供参考。The tropomyosin receptor kinase(TRK) family of receptor tyrosine kinases encoded by NTRK genes play an important role in the development and normal functioning of the nervous system. NTRK fusions are oncogenic drivers of various adult and pediatric cancers. Therefore, TRKs inhibitors have attracted extensive attention with intensive investigation in the past decade. The successful approval of the first-generation TRK inhibitors, larotrectinib and entrectinib, was of monumental significance. As with other tyrosine-kinase inhibitors, resistance can develop over time in patients receiving TRK inhibitors. Therefore, solving drug resistance and multiple mutations will be the focus of future research & development. This review summarizes the recent reports and development of small-molecule TRK inhibitors with different chemotypes and their activity and selectivity to provide reference for the further development of novel TRK inhibitors.

关 键 词：原肌球蛋白受体激酶 抑制剂 神经受体酪氨酸激酶基因 神经受体酪氨酸激酶基因融合癌 

分 类 号：R730.5[医药卫生—肿瘤]