Recent progress of targeted small molecular CDK9 degraders based on PROTAC technology
10.16438/j.0513-4870.2022-0442
- VernacularTitle:基于PROTAC技术的靶向CDK9小分子降解剂的研究进展
- Author:
Jin-xiu LI
;
He-wei DONG
;
Wei HOU
- Publication Type:Research Article
- Keywords:
cyclin-dependent kinases 9;
proteolysis-targeting chimera;
inhibitor;
antitumor;
egradation
- From:
Acta Pharmaceutica Sinica
2022;57(9):2696-2708
- CountryChina
- Language:Chinese
-
Abstract:
CDKs proteins are a kind of cell cycle protein-dependent kinases, which serve as important roles in controlling cell division and transcriptional stages. Among them, CDK9, as a key regulator responsible for the transcriptional elongation of cells, drives the development of various malignant cells and is considered as an important target in the field of anti-tumor drug development. However, the CDK family proteins feature high conservativeness and similarity in structure, leading to the poor selectivity and severe side effects for traditional small-molecular CDK9 inhibitors, which has limited their clinical applications. In view of this, there is an urgent need to investigate CDK9 targets through a novel strategy. The PROTAC is an emerging drug discovery strategy that the degrader could specifically recognize the target protein through indirect linkage with ubiquitin ligases and ultimately eliminate the target protein through the ubiquitination degradation system. This paper provides a brief overview of the structure and function of CDK9 protein, its relationship with the poor prognosis of clinical diseases, as well as the currently reported small molecular inhibitors. The latest research progress on the targeted degradation of CDK9 protein based on PROTAC technology is highlighted. Finally, the development prospects of this target protein in this novel technology field are summarized and prospected, aiming to provide a reference for the development of antitumor drugs in this direction.
