PROTAC (proteolysis-targeting chimeras), which selectively degrades target proteins, has become the most popular technology for drug development in recent years. Here, we introduce the history of PROTAC, and summarize the recent advances in novel types of degradation technologies based on the PROTAC mechanism, including TF-PROTAC, Light-controllable PROTAC, PhosphoTAC, LYTAC, AUTAC, ATTEC, CMA, RNA-PROTAC and RIBOTACs. In addition, the clinical progress, current challenges and future prospects of degradation technologies based on PROTAC mechanism are discussed.

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