Drugtamer‐PROTAC Conjugation Strategy for Targeted PROTAC Delivery and Synergistic Antitumor Therapy

• DOI: 10.1002/advs.202401623
• Publication Date: 2024-04-19T11:15:53Z
• Authors: Shipeng He; Yuxin Fang; Yaojin Zhu; Ziyang Ma; Guoqiang Dong; Chunquan Sheng
• Keywords: Linker

Abstract Proteolysis‐targeting chimeras (PROTACs) have emerged as a promising strategy for targeted protein degradation and drug discovery. To overcome the inherent limitations of conventional PROTACs, an innovative drugtamer‐PROTAC conjugation approach is developed to enhance tumor targeting antitumor potency. Specifically, smart prodrug designed by conjugating “drugtamer” nicotinamide phosphoribosyltransferase (NAMPT) PROTAC using microenvironment responsible linker. The consists fluorouridine nucleotide DNA‐like oligomer. Compared NAMPT combination + fluorouracil, AS‐2F‐NP demonstrates superior targeting, efficient cellular uptake, improved in vivo potency reduced side effects. This study provides precise delivery synergistic agents.