PROTAC

Also known as: Proteolysis-Targeting Chimera

A bifunctional molecule that recruits the cell's protein-degradation machinery to destroy a target protein.

Definition

A Proteolysis-Targeting Chimera (PROTAC) is a heterobifunctional small molecule with two ligands joined by a linker — one binds a target protein, the other recruits an E3 ubiquitin ligase (e.g. cereblon, VHL). The target is then polyubiquitinated and degraded by the proteasome. PROTACs enable "undruggable" target degradation. ARV-471 (vepdegestrant, Arvinas/Pfizer) was the first PROTAC in Phase 3.

See also

Other pharmacology terms