分子胶药物活性测定方法的研究进展

Research advances in methods for determining the activity of molecular glue drugs

摘要

分子胶药物通过诱导或稳定蛋白-蛋白相互作用来发挥药理作用。对其进行活性评价除了需要评估它们与蛋白间的结合能力以外，还需评估三元复合物形成、界面稳定性、协同性和细胞内功能等多个方面。本文从体外定量检测、细胞学验证、理论计算与模拟等三个方面，对目前常用的分子胶活性评价方法及其应用进行总结；并结合药物研发过程对活性评价工作效率的实际需求，提出了分层次活性评估的方法，以期为分子胶药物活性研究和方法选择提供参考。

Abstract

Molecular glue drugs exert pharmacological effects by inducing or stabilizing protein-protein interactions. Evaluating their activity not only requires assessing their binding to proteins, but also involves the evaluation of multiple aspects such as ternary complex formation, interface stability, cooperativity, and intracellular function. This review summarizes the commonly used methods and applications for evaluating the activity of molecular glues from three aspects: in vitro quantitative detection, cellular validation, and theoretical calculations and simulations; and proposes a hierarchical approach to activity evaluation based on the actual needs for efficiency in drug development, aiming to provide some reference for the study of molecular glue drug activity and the selection of evaluation methods.

关键词

分子胶药物 / 活性评价 / 蛋白-蛋白相互作用 / 生物物理检测 / 理论预测

Key words

molecular glue drugs / activity assessment / protein-protein interactions / biophysical assays / theoretical prediction

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基金资助

江苏省自然科学基金项目(BK20211254)

教育部产学合作协同育人项目(231103177201655)