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A Review of Proteolytic Targeting Chimeras
The concept of proteolytic targeting chimera (PROTAC) was first proposed by Crews and Deshaies laboratory in 2001, the team successfully achieved the degradation of methionyl aminopeptidase 2 (MetAp-2) by PROTAC method. Since then, PROTACs targeting androgen receptor (AR) and estrogen receptor (ER) have appeared one after another. In 2004, a PROTAC molecule that recruited the tumor suppressor protein VHL through a polypeptide fragment on HIF1-α showed a greater improvement in membrane permeability and could also exist stably in cells. However, these peptide-based PROTAC molecules were not ready for drug preparation. Until 2008, when the first small-molecule E3 ubiquitinase ligand-based PROTAC came out, marking the beginning of small-molecule PROTAC research, and…