Fig. 2.

Schematic representation of the PROTAC mode of action. POI: protein of interest – the protein that is meant to be degraded. E3 denotes the E2/E3 ligase complex, commonly VHL, CRBN, cIAP1 or MDM2. The bifunctional molecule links together a ligand for the POI, and an E3 ligase binder. The induced proximity between the ligase and protein of interest leads to poly-ubiquitination (Ub) of the POI, which triggers its proteasomal degradation. The released PROTAC can exert its function again, which gives rise to a catalytic mode of action.