Abstract

Chemotherapeutic strategies that target irregularly produced or mutant proteins using monoclonal antibodies (mAbs) and tiny molecular inhibitors have been extensively employed to target cancer. However, because most intracellular proteins lack antigens or active sites with which mAbs or SMIs can engage, they have not been considered druggable targets. After extensive research, PROTACs (Proteolysis Targeting chimaeras) have become a promising way to work with proteins. Scaffolding proteins and transcription factors may also be targeted. The present targets of PROTACs include kinases like CDKs and RTKs, overexpressed oncogenic proteins like AR and BRDs, cancer-driven mutant proteins like EGFR, and disease-relevant fusion proteins like NPM/EML4-ALK and BCR-ABL. The inability of small-molecule intracellular degraders to enter cells and their low bioavailability can also be circumvented with PROTABs. The use of multispecific binding proteins is an improved way to target the breakdown of membrane- bound and cell-surface proteins.

Keywords: PROTAB, PROTAC, cancer, E3 ubiquitin ligase, TRIM21, SMI’s