Proteolysis-targeting chimeras for targeting protein for degradation.

Abstract

Proteolysis-targeting chimeras (PROTACs) are an emerging tool for therapeutic intervention by reducing or eliminating disease-causing proteins. PROTACs are bifunctional molecules that consist of a target protein ligand, a linker and an E3 ligase ligand, which mediate the polyubiquitination of the target protein, ultimately leading to the target protein degradation by the ubiquitin-proteasome pathway. We review some of the main PROTACs that have been reported recently and discuss their potential therapeutic benefits over classical enzyme inhibition. Future research is expected to focus on the delivery and bioavailability of PROTACs due to their high molecular weight (700-1000Da).