Synthesis, evaluation and proteomic analysis of PROTAC based on parthenolide
10.16438/j.0513-4870.2023-0228
- VernacularTitle:小白菊内酯降解剂的设计、合成及生物学研究
- Author:
Tong GAO
1
;
Wen-tao ZHANG
2
;
Shan-shan SONG
3
;
Di ZHOU
1
;
Tong-chao LIU
3
;
Ze-hong MIAO
3
;
Bing XIONG
3
Author Information
1. Anhui University of Chinese Medicine, Hefei 230031, China
2. Shenyang Pharmaceutical University, Shenyang 110016, China
3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
parthenolide;
PROTAC;
target;
antitumor;
proteomics
- From:
Acta Pharmaceutica Sinica
2023;58(9):2715-2726
- CountryChina
- Language:Chinese
-
Abstract:
As a natural product with a long history of medicinal use, parthenolide has aroused great interest of chemists and biologists. Existing studies have shown that it has anti-inflammatory, antitumor and other pharmacological activities, and also revealed its action on NF-κB signaling pathway, DNMT1 enzyme and Wnt/β-catenin signaling pathway. But its biological targets remain to be elucidated systematically. Proteolysis Targeting Chimeras (PROTAC) provides a new strategy for target discovery of natural products, which can be used to explore the panorama of protein changes in cells through proteomic investigation, so as to analyze their potential targets. Based on this idea, current study designed and synthesized 20 parthenolide-derived degraders. After measured their antitumor activity in vitro, selected compounds were carried out the proteomic experiment. Finally, 139 down-regulated differentially expressed proteins were identified and the discovery of parthenolide interacting protein was preliminarily explored.
