A PROTAC ligand is a specialized molecule that acts as one of the two "sticky ends" of a PROTAC (PROteolysis-TArgeting Chimera), a class of drugs designed to destroy disease-causing proteins rather than just inhibiting them.
PROTAC molecule is heterobifunctional, with two different binding heads connected by a flexible chemical linker:
While there are over 600 E3 ligases in the human body, most current PROTACs utilize ligands for just a few well-studied ones Cereblon (CRBN) Ligands, VHL Ligands, MDM2 (using nutlins) and IAP (using bestatin derivatives).
As of 2026, several PROTACs using these ligands, such as Vepdegestrant (ARV-471) for breast cancer and BMS-986365 for prostate cancer, have advanced into Phase 3 clinical trials.