化学诱导临近效应和分子胶药物  

Chemically induced proximity and molecular glue

作　　者：郭宗儒[1] GUO Zong-ru(Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2024年第4期789-800,共12页Acta Pharmaceutica Sinica

摘　　要：生物界存在的化学诱导临近效应是维持机体和细胞功能的重要方式,近年来诱导临近在医药领域受到了重视和应用,分子胶和蛋白靶向降解嵌合体(PROTAC)在肿瘤和免疫性疾病的治疗得到广泛的研究。分子胶和PROTAC促进两个蛋白相互靠近,诱导契合发生三元体的互补性结合,并激发目标蛋白的降解和调节信号转导。分子胶药物作用机制与传统小分子药物不同,犹如催化剂样作用促进两个蛋白的相互作用使病理性靶标蛋白降解而失活。本文从药物化学视角对处于临床研究的某些分子胶的研制过程、结构特征和作用特点作简要的讨论。The chemically induced proximity(CIP)in biological realm is an important way to maintain the function of organism and cells.In recent years,CIP has been paid attention to and applied in the field of bio-medicines.Molecular glue and PROTAC are widely investigated for the treatment of tumors and immunopathy.Based upon the CIP principle molecular glue and PROTAC promote two proteins to approach each other,induce the complementary binding to triads,and then degrade the target protein or regulate functions.Different from conventional drugs,molecular glue acts as a catalyst,which induces two proteins to approach,bind and ubiquitinate,without taking part in the subsequent degradation process,so it can theoretically function in an infinite cycle.In this article,the development process,structural characteristics and functional characteristics of some molecular glues in clinical trials are briefly discussed from the viewpoint of medicinal chemistry.

关 键 词：诱导临近 分子胶 三元复合物 泛素-蛋白酶体系统 

分 类 号：R914[医药卫生—药物化学]