摘要
蛋白降解靶向嵌合体(proteolysis targeting chimeria,PROTAC)通过利用泛素蛋白酶体途径实现对靶蛋白降解,颠覆了传统小分子抑制剂的理念。在非小细胞肺癌(non-small cell lung cancer,NSCLC)常见的突变靶点中,PROTAC技术在临床前研究中已经成功实现了鼠类肉瘤病毒癌基因(kirsten rat sarcoma viral oncogene homolog,KRAS)、表皮生长因子受体(epidermal growth factor receptor,EGFR)和间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)等蛋白的有效降解。PROTAC药物以其事件驱动的独特优势,有望克服小分子抑制剂产生的获得性耐药的问题,并对难成药靶点展现出良好的治疗潜力,有望成为NSCLC治疗的新策略。
Proteolysis targeting chimeria(PROTAC)degrades target proteins by utilizing the ubiquitin-proteasome pathway,subverting the concept of traditional small molecule inhibitors.Among the common mutation targets of non-small cell lung cancer(NSCLC),PROTAC technology has successfully achieved the effective degradation of kirsten rat sarcoma viral oncogene homolog(KRAS),epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK)and other proteins in preclinical studies.PROTAC drugs with their unique event-driven advantages,are expected to overcome acquired drug resistance caused by small molecule inhibitors and show good therapeutic potential for undruggable targets,thereby providing a new strategy for the treatment of NSCLC.
作者
姜琳
张敬博
胡嘉淇
齐海翔
许恒
Lin JIANG;Jingbo ZHANG;Jiaqi HU;Haixiang QI;Heng XU(Institute of Materia Medica,Chinese Academy of Medical Sciences,Beijing 100050,China)
出处
《中国肺癌杂志》
CAS
CSCD
北大核心
2022年第7期477-481,共5页
Chinese Journal of Lung Cancer
基金
中国医学科学院医学与健康科技创新工程基金(No.2021-I2M-1-026)
中央高校基本科研业务费专项资金(No.3332019149)资助。
