Early evaluation of opportunities in oral delivery of PROTACs to overcome their molecular challenges

被引：7
|
作者：
Yang, Wenzhan [1 ]
Saboo, Sugandha [1 ]
Zhou, Liping [1 ]
Askin, Sean [2 ]
Bak, Annette [1 ]
机构：
[1] AstraZeneca, Adv Drug Delivery, Pharmaceut Sci, R&D, Boston, MA 02451 USA
[2] AstraZeneca, Adv Drug Delivery, Pharmaceut Sci, R&D, Cambridge, England
来源：
DRUG DISCOVERY TODAY | 2024年 / 29卷 / 02期
关键词：
drug delivery; PROTAC; drug discovery; lipid-based formulations (LBF); amorphous solid dispersions (ASDs); LIPID-BASED FORMULATIONS; WATER-SOLUBLE DRUGS; PRECIPITATION INHIBITORS; CYCLOSPORINE-A; SYSTEMS; ABSORPTION; BIOAVAILABILITY; CLASSIFICATION; SOLUBILITY; PERMEABILITY;
D O I：
10.1016/j.drudis.2023.103865
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
PROteolysis TArgeting Chimeras (PROTACs) offer new opportunities in modern medicine by targeting proteins that are intractable to classic inhibitors. Heterobifunctional in nature, PROTACs are small molecules that offer a unique mechanism of protein degradation by hijacking the ubiquitin-mediated protein degradation pathway, known as the ubiquitin-proteasome system. Herein, we present an analysis on the structural characteristics of this novel chemical modality. Furthermore, we review and discuss the formulation opportunities to overcome the oral delivery challenges of PROTACs in drug discovery.
引用
收藏
页数：12
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