Advances in small molecule inhibitors of ACK1
10.16438/j.0513-4870.2019-0831
- VernacularTitle:ACK1小分子抑制剂的研究进展
- Author:
Xiao-fei ZHOU
1
;
Rui LI
1
;
Hong-juan YAO
1
;
Liang LI
1
Author Information
1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
activated Cdc42-associated kinase;
targeted anti-cancer drug;
non-receptor tyrosine kinase;
small molecule inhibitor
- From:
Acta Pharmaceutica Sinica
2020;55(5):821-831
- CountryChina
- Language:Chinese
-
Abstract:
ACK1 (activated Cdc42-associated kinase) is a non-receptor tyrosine kinase, originally identified by its binding to the GTP-binding small GTPase Cdc42. It is widely expressed in human tissues and activated by various extracellular growth factors such as EGF, PDGF and TGF-β. The activated ACK1 mediates the signaling cascade by interacting with downstream effectors followed by their phosphorylation. In recent years, researchers have investigated the biological functions of ACK1 and its roles in cancer research. The gene amplification and overexpression of ACK1 is associated with a poor prognosis and metastasis in a variety of cancers including lung, ovarian and prostate cancers. Therefore, the development of small molecule inhibitors of ACK1 provides promising opportunities for cancer-targeted therapy. In this review, we briefly describe recent advances in understanding the activation and biological function of ACK1 and introduce its novel inhibitors with potential therapeutic activities in preclinical studies.
