Design, synthesis and degradation activity of BRD4-targeting ATTECs / 药学实践与服务
Journal of Pharmaceutical Practice and Service
; (12): 18-25, 2023.
Article
ي Zh
| WPRIM
| ID: wpr-953753
المكتبة المسؤولة:
WPRO
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.
النص الكامل:
1
الفهرس:
WPRIM
اللغة:
Zh
مجلة:
Journal of Pharmaceutical Practice and Service
السنة:
2023
نوع:
Article