布鲁顿酪氨酸激酶抑制剂靶点占有率评价方法的研究进展  

Advance in Target Occupancy Evaluation Methods for Bruton's Tyrosine Kinase Inhibitors

作　　者：霍一凡 刘丹 满素勤 邱云良 HUO Yifan;LIU Dan;MAN Suqin;QIU Yunliang(China State Institute of Pharmaceutical Industry Co.,Ltd.,Shanghai 201203;Shanghai InnoStar Bio-Tech Co.,Ltd.,Shanghai 201203)

机构地区：[1]中国医药工业研究总院有限公司,上海201203 [2]上海益诺思生物技术股份有限公司,上海201203

出　　处：《中国医药工业杂志》2025年第1期38-46,共9页Chinese Journal of Pharmaceuticals

基　　金：上海市科委工程技术研究中心专项项目(17DZ2252900)。

摘　　要：布鲁顿酪氨酸激酶(BTK)在B细胞的发育、增殖、分化、活化和细胞因子分泌等方面发挥着关键作用。BTK抑制剂(BTKI)通过阻断BTK或抑制其活性而有效阻断下游细胞信号转导和受体活化,并对与多种疾病发生、发展相关的上游信号分子产生负反馈作用,以发挥治疗作用。在BTKI的研发过程中,靶点占有率作为衡量药物与BTK结合能力的指标,已成为临床前和临床研究中药效学评价的重要参数,不仅可以反映给药剂量与靶点占有率之间的关系,对于建立药效与靶点占有率之间的联系也有重要意义。文章对BTKI靶点占有率的评价方法进行综述,并讨论不同方法的优缺点,以期为BTKI研发过程中选择合适的靶点占有率评价方法提供参考。Bruton's tyrosine kinase(BTK)plays a crucial role in the development,proliferation,differentiation,activation and cytokine secretion of B cells.BTK inhibitors(BTKIs)can effectively block downstream cell signaling and receptor activation by blocking BTK or inhibiting its activity,and produce negative feedback on upstream signaling molecules related to the occurrence and development of various diseases,so as to playing a therapeutic role.In the research and development of BTKIs,the target occupancy,serving as an evaluation indicator of the binding affinity of drugs to BTK,has become an important pharmacodynamic parameter in preclinical and clinical studies.Besides,it not only reflects the relationship between dose and target occupancy,but also has important significance for establishing the relationship between efficacy and target occupancy.This paper reviews the evaluation methods of BTKI target occupancy,and discusses the advantages and disadvantages of these methods,aiming to provide some references for selecting suitable target occupancy evaluation methods in the research and development process of BTKI.

关 键 词：布鲁顿酪氨酸激酶(BTK) BTK抑制剂 信号转导 靶点占有率 研究进展 

分 类 号：R917[医药卫生—药物分析学] R96[医药卫生—药学]