连接器
泛素连接酶
蛋白酶体
药物发现
蛋白质水解
化学
药代动力学
流出
DNA连接酶
细胞通透性
计算生物学
组合化学
药理学
泛素
生物化学
生物
计算机科学
酶
操作系统
基因
作者
Carlotta Cecchini,Sébastien Tardy,Léonardo Scapozza
出处
期刊:Chimia
日期:2022-04-27
卷期号:76 (4): 341-341
被引量:6
标识
DOI:10.2533/chimia.2022.341
摘要
Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional molecules that act as degraders. They selectively remove disease-associated proteins by hijacking the Ubiquitin-Proteasome System (UPS). Chemically, they consist of three parts: an E3 ligase ligand, a target of interest (TOI) ligand, and a linker, which connects the two moieties. The rapid expansion of PROTAC Technology as an innovative therapeutic modality in cancer fostered the drug discovery effort to optimize their physicochemical properties. Due to their large size, their features are far from the traditional ‘drug-like’ properties. This short review highlights some of the structural modifications in the linker component to optimize the PROTAC Drug Metabolism and Pharmacokinetics (DMPK) profile. In particular, we discussed aspects related to solubility, cell permeability, active transporters efflux and, metabolic stability.
科研通智能强力驱动
Strongly Powered by AbleSci AI