Advances in developing small molecule inhibitors of ubiquitin-specific protease 1
10.16438/j.0513-4870.2023-1076
- VernacularTitle:靶向泛素特异性蛋白酶1小分子抑制剂的研究进展
- Author:
Jia-hao XU
1
,
2
,
3
;
Hong-rui LI
2
,
3
,
4
;
Rui-xian BA
2
,
3
,
4
;
Tong-chao LIU
5
;
Bing XIONG
3
,
5
Author Information
1. School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
3. Yangtze Delta Drug Advanced Research Institute, Nantong 226133, China
4. Shenyang Pharmaceutical University, Shenyang 110016, China
5. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
ubiquitin-specific protease 1;
small molecule inhibitor;
synthetic lethality;
rug resistance;
structure-activity relationship
- From:
Acta Pharmaceutica Sinica
2024;59(4):866-885
- CountryChina
- Language:Chinese
-
Abstract:
Ubiquitin-specific protease 1 (USP1) is one of the deubiquitinating enzymes which has received increasing attention in cancer research. USP1 is overexpressed in many types of cancer cells, and has been found to control tumorigenesis and progression by regulating various proteins associated with tumors, such as SIK2, GSK-3β, and Bcl-2. Knockdown or pharmacological inhibition of USP1 can effectively suppress tumors and is also expected to address the issues of cisplatin and poly ADP-ribose polymerase (PARP) inhibitor resistance. This review describes the structure and function of USP1 and the relationship between USP1 targets and tumors and systematically summarizes the structure-activity relationships of small molecule USP1 inhibitors disclosed from 2013 to 2023. Finally, this review discusses the challenges and opportunities in developing small molecule USP1 inhibitors.
