Advances in antitumor research of bifunctional small molecule inhibitors targeting heat shock protein 90
10.16438/j.0513-4870.2023-0388
- VernacularTitle:靶向热休克蛋白90的双功能小分子抑制剂的抗肿瘤研究进展
- Author:
Hong-ping ZHU
1
;
Xin XIE
1
;
Rui QIN
1
;
Wei HUANG
1
;
Yan-qing LIU
1
;
Cheng PENG
1
;
Gu HE
2
;
Bo HAN
1
Author Information
1. State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
2. West China Hospital, Sichuan University, Chengdu 610041, China
- Publication Type:Research Article
- Keywords:
Hsp90;
omain;
biological function;
ual inhibitor;
antitumor activity
- From:
Acta Pharmaceutica Sinica
2024;59(1):1-16
- CountryChina
- Language:Chinese
-
Abstract:
The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.
