蛋白降解靶向嵌合体技术在血液肿瘤中的应用  

Application of PROTACs in Hematological Malignancies——Review

作　　者：贾艳楠 秘营昌 JIA Yan-Nan;MI Ying-Chang(Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,State Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Tianjin 300020 China)

机构地区：[1]中国医学科学院血液病医院(中国医学科学院血液学研究所),实验血液学国家重点实验室,国家血液系统疾病临床医学研究中心,细胞生态海河实验室,天津300020

出　　处：《中国实验血液学杂志》2023年第6期1921-1924,共4页Journal of Experimental Hematology

摘　　要：蛋白降解靶向嵌合体(PROTAC)是一种利用细胞内泛素蛋白酶体系统选择性降解靶蛋白的“异双功能”小分子药物。因其独特的作用机制、靶向“不可成药”和突变肿瘤蛋白、组织特异性等优势在肿瘤药物开发中发挥出巨大的潜力。一系列靶向在血液系统恶性肿瘤发生发展中起关键作用的蛋白的PROTAC已经相继被开发,特别是针对BCL-XL、IRAK4、STAT3和BTK等靶点的PROTAC已进入临床试验阶段。本文将对靶向血液系统肿瘤常见靶点的PROTAC在临床前或者临床试验中取得的研究成果进行综述。Proteolysis-targeting chimeras(PROTACs) are heterobifunctional small molecules by utilizing the ubiquitin proteasome system(UPS) to degrade proteins of interest.PROTACs have exhibited unprecedented efficacy and specificity in degrading various oncogenic proteins because of their unique mechanism of action,ability to target “undruggable” and mutant proteins.A series of PROTACs have been developed to degrade multiple key protein targets for the treatment of hematologic malignancy.Notably,PROTACs that target BCL-XL,IRAK4,STAT3 and BTK have entered clinical trials.The known PROTACs that have the potential to be used to treat various hematological malignancies are systematically summarized in this review.

关 键 词：蛋白降解靶向嵌合体 血液肿瘤 靶点 蛋白酶体系统 

分 类 号：R733[医药卫生—肿瘤]