The state of the art of PROTAC technologies for drug discovery

Protein degradation technology has progressed dramatically since 2001 when proteolysis targeting chimera (PROTAC) was first reported. Various of distinctive degradation technologies based on PROTAC have been developed for the degradation of kinases, nuclear receptors, epigenetic proteins, misfolded proteins, and also RNAs, etc. These technologies greatly broaden the spectrum of targets and the scope of clinical applications for the treatment of cancer, neurodegenerative diseases and virus diseases, etc. More than 15 targeted degraders have been in the clinic to date. Here in this review, we summarized the constituents and examples of different degradation strategies, as well as their advantages and limitations.