Advances of targeted protein degradation technology and its applications in diseases therapy.
- Author:
Shuping CHEN
1
;
Han YANG
1
;
Jinlu JIANG
1
;
Siyuan YU
1
;
Tingdong LI
1
;
Shengxiang GE
1
Author Information
- Publication Type:Review
- Keywords: disease therapy; lysosomal degradation pathway; proteolysis targeting chimeras (PROTAC); ubiquitin-proteasome system
- MeSH: Animals; Proteasome Endopeptidase Complex/metabolism*; Protein Processing, Post-Translational; Proteins/metabolism*; Proteolysis; Technology
- From: Chinese Journal of Biotechnology 2021;37(11):3915-3932
- CountryChina
- Language:Chinese
- Abstract: Targeted protein degradation (TPD) technology facilitates specific and efficient degradation of disease-related proteins through hijacking the two major protein degradation systems in mammalian cells: ubiquitin-proteasome system and lysosome pathway. Compared with traditional small molecule-inhibitors, TPD-based drugs exhibit the characteristics of a broader target spectrum. Compared with techniques interfere with protein expression on the gene and mRNA level, TPD-based drugs are target-specific, efficaciously rapid, and not constrained by post-translational modification of proteins. In the past 20 years, various TPD-based technologies have been developed. Most excitingly, two TPD-based therapeutic drugs have been approved by FDA for phase Ⅰ clinical trials in 2019. Despite of the early stage characteristics and various obstructions of the TPD technology, it could serve as a powerful tool for the development of novel drugs. This review summarizes the advances of different degradation systems based on TPD technologies and their applications in disease therapy. Moreover, the advantages and challenges of various technologies were discussed systematically, with the aim to provide theoretical guidance for further application of TPD technologies in scientific research and drug development.
