Cancer Cell Research (Online ISSN: 2161-2609)

Cancer Cell Research 2021 8(30) 795-806; published online  29 November 2021

Abstract: Proteolysis-targeting chimeras technology has emerged as a new therapeutic strategy that take advantage of endogenous ubiquitin-proteasome system (UPS) to selectively degrade oncoproteins. It has been developed from peptide-based PROTACs to small molecule-based ones, with capability to degrade a variety of target proteins with unprecedented advantages compared with traditional inhibitors. PROTACs have attracted the interest of both academia and industry and developed rapidly in the past decades. To date, there has been approximately 13 drugs already entered the clinic. However, as a new technology, it is facing many problems and challenges as well.
This review will begin with introduction of common structure and rational design of PROTACs, with concentration on their significant features compared with traditional inhibitors. Then, different types of PROTACs will be discussed, followed by brief description of PRATACs that have reached the clinical stage.