From PROTAC to TPD: Advances and Opportunities in Targeted Protein Degradation

Abstract

PROTAC is a rapidly developing engineering technology for targeted protein degradation using the ubiquitin–proteasome system, which has promising applications for inflammatory diseases, neurodegenerative diseases, and malignant tumors. This paper gives a brief overview of the development and design principles of PROTAC, with a special focus on PROTAC-based explorations in recent years aimed at achieving controlled protein degradation and improving the bioavailability of PROTAC, as well as TPD technologies that use other pathways such as autophagy and lysosomes to achieve targeted protein degradation.

Keywords

• PROTAC
• TPD
• targeted protein degradation
• protein-hydrolysis-targeted chimeras
• ubiquitin–proteasome system