非修饰靶点发现细胞热位移分析技术的变革与应用进展  

The evolution and application progress of non-modified drug target discovery CETSA technology

作　　者：刘广苑 李亚慧 张炜 孔德志[1] LIU Guang-yuan;LI Ya-hui;ZHANG Wei;KONG De-zhi(Institute of Integrated Traditional Chinese and Western Medicine,Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北医科大学中西医结合研究所,河北石家庄050017

出　　处：《药学学报》2024年第1期25-34,共10页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82174004);国家重点研发计划“中医药现代化”重点专项(2022YFC3500501)。

摘　　要：了解药物的蛋白靶点研究方法对于新药研发、药物的临床应用、药物的作用机制和疾病的致病机制都具有十分重要的意义。细胞热位移分析(cellular thermal shift assay,CETSA)作为无修饰分析的靶点研究方法自开发以来就被广泛应用。经过不断地演化,现在已经出现了多种基于CETSA的技术结合,如基于质谱的细胞热位移分析(mass spectrometry-based cellular thermal shift assay,MS-CETSA)、结合等温剂量反应实验的细胞热位移分析(isothermal dose response-cellular thermal shift assay,ITDR-CETSA)、结合均相光激化学发光免疫分析的细胞热位移分析(amplified luminescent primity homogeneous assay-cellular thermal shift assay,Alpha-CETSA)等。这些技术融合了各自的优势,进一步扩展了CETSA的应用范围,适用于从药物筛选到监测药物在患者体内的靶点结合和脱靶毒性研究的整个药物开发链。本文结合作者的研究经验,综述了近年来CETSA和相关结合技术的原理及其在靶点发现上的应用、数据处理分析的进展,旨在为CETSA的进一步应用提供参考和借鉴。Understanding the research methods for drug protein targets is crucial for the development of new drugs,clinical applications of drugs,drug mechanisms,and the pathogenesis of diseases.Cellular thermal shift assay(CETSA),a target research method without modification,has been widely used since its development.Now,there are various CETSA-based technology combinations,such as mass spectrometry-based cellular thermal shift assay(MS-CETSA),isothermal dose response-cellular thermal shift assay(ITDR-CETSA),amplified luminescent proximity homogeneous assay-cellular thermal shift assay(Alpha-CETSA),etc.,which combine their respective advantages and further expand the application scope of CETSA.These technologies are suitable for the entire drug development chain,from drug screening to monitoring the target binding and off-target toxicity of drugs in patients.Based on the author's research experience,this paper reviews the principles of CETSA and related binding technologies,their application in target discovery,and the progress of data processing and analysis in recent years,aiming to provide reference and reference for the further application of CETSA.

关 键 词：细胞热位移分析 热蛋白质组分析 靶点发现 技术结合 

分 类 号：R914[医药卫生—药物化学]