A Review on Targeted Protein Degradation and Its Novel Therapeutic Approaches

A new concept of drug development is drug-induced degradation of a target protein. Protein degradation is one of the cell's methods for permanently inactivating proteins. The Ubiquitin-Proteasome System (UPS) and autophagy are two main intracellular protein degradation pathways in eukaryotes. Autophagy has been shown to be induced by inhibiting proteasomal activities, suggesting a coordinated and complementary relationship between these two mechanisms. However, little is known about autophagy's function in UPS control. Various targeted protein degradation pathways, such as PROTACs, Degradation TAG System, Auxin inducible degron, DeGraff and ZIF1 proteolytic systems, and therapeutic approaches based on protein degradation, have been shown in this study. We have also addressed PROTACS, which target cancer-related targets for cancer therapy, in this study.