Design, synthesis and degradation activity of BRD4-targeting ATTECs
10.12206/j.issn.2097-2024.202206050
- VernacularTitle:靶向BRD4的ATTECs设计、合成与降解活性研究
- Author:
Luozhu ZHOU
1
;
Chunquan SHENG
1
Author Information
1. Department of Medicinal Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
- Keywords:
autophagosome-tethering compounds;
BRD4;
LC3;
Ispinesib
- From:
Journal of Pharmaceutical Practice
2023;41(1):18-25
- CountryChina
- Language:Chinese
-
Abstract:
Objective To design and synthesize autophagic degraders targeting BRD4 based on autophagosome tethering compound (ATTEC) strategy and test their BRD4 degradation activity. Methods BRD4-targeting ATTECs were constructed by conjugating ispinesib that used as a LC3 ligand and JQ1 through a variety of alkane linkers. The final compounds were confirmed by 1H NMR, 13C NMR and ESI-MS, and their degradation activity in different cell lines were tested by Western Blot. Results Five BRD4-ATTEC molecules were successfully synthesized for the first time. Compound 4 showed moderate BRD4 degradation activity in different cell lines. Conclusion The novel BRD4 autophagic degraders were discovered, which expanded the applicability of targeted autophagic degradation via ATTEC.
