Recent progress in targeting degradation of FAK based on PROTAC
10.16438/j.0513-4870.2020-1990
- VernacularTitle:基于PROTAC技术靶向降解FAK蛋白的研究进展
- Author:
Ying-ruo XU
;
Qin-song ZHANG
;
Jing-yi WU
;
Run-fei BAO
;
Shen-xin ZENG
- Publication Type:Research Article
- Keywords:
local focal adhesion kinase;
proteolysis targeting chimera;
small molecule inhibitor;
E3 ligase;
rug development
- From:
Acta Pharmaceutica Sinica
2021;56(6):1571-1579
- CountryChina
- Language:Chinese
-
Abstract:
Local focal adhesion kinase (FAK) is a non-receptor intracellular tyrosine kinase that plays an important role in tumor initiation, development, metastasis and invasion, and is considered to be an important target for the development of antineoplastic drugs. It has both kinase-dependent and non-kinase-dependent scaffolding functions. However, traditional small molecular inhibitors can only inhibit its kinase-dependent activity, so it is difficult to target the kinase-independent scaffolding function. Therefore, there is an urgent need for novel strategies to enhance FAK targeting to lay the foundation for determining the druggability and discovery of FAK inhibitors. Proteolysis targeting chimera (PROTAC) is a new drug development strategy that can recruit E3 ligase to specifically ubiquitinylate target proteins for degradation through the proteasome system. The unique mechanism of action of the PROTAC system could be used to target and degrade the FAK protein, thus eliminating the scaffolding function of FAK. In this review, FAK protein, the signaling pathway, and small molecule inhibitors are briefly described, and the latest research progress in targeting the degradation of FAK using PROTAC technology is summarized.
