PROTACS: A technology with a gold rush-like atmosphere

Abnormally expressed or malfunctioning proteins may affect or even damage cells, leading to the onset of diseases. Proteolysis targeting chimera (PROTAC) technology has been proven to be a fresh therapeutic strategy, superior to conventional small molecule inhibitors for the treatment of diseases caused by pathogenic proteins. Unlike conventional small molecule inhibitors that are occupancy-driven, PROTACs are heterobifunctional small molecules with catalytic properties. They combine with E3 ligases and target proteins to form a ternary complex, rendering the target protein ubiquitous and subsequently degraded by the proteasome. This paper focuses first on significant events in the development of PROTAC technology from 2001 to 2022, followed by a brief overview of various PROTACs categorized by target proteins. In addition, the applications of PROTACs in the treatment of diseases and fundamental biology are also under discussion. [Display omitted] •Focusing on major events in PROTAC technology from 2001 to 2022.•Using the classification of FDA-approved kinase inhibitors as a criterion.•The applications of PROTACs are under discussion.•Containing thoughts on ADME for PROTACs.