PROTACs: Novel approach for cancer breakdown by breaking proteins.

Ubiquitination defects have been reported in various diseases, including neurodegenerative diseases, metabolic disorders and cancer. Balance between degradation and synthesis of the proteins to treat cancer can be managed by designing a chimeric molecule, known as Proteolysis Targeting Chimeric molecule (Lee, Kim et al. 2021). Proteolysis-targeting chimeras (PROTACs) acts as a tool for conducting therapeutic intervention. It eradicates or reduces the proteins that are responsible for causing diseases. Each PROTAC contains a target warhead, an E3 ligand and a linker. E3 ligases are recruited by these bifunctional molecules, and the Ubiquitin (Ub) Proteasome System (UPS) is used to target the degradation of specific proteins. As compared to inhibition, this degradation offers several advantages in the drug resistance, selectivity, and potency. Thus, numerous small molecule PROTACs are identified so far. In this review, the development of PROTACs, historical milestones, the biological mechanism, advantages and recent progress, and role of PROTAC in prostate cancer, breast cancer, non-hodgkin lymphoma, multiple myeloma, and malignant peripheral nerve sheath tumors are summarized.