A critical and necessary step to design a potent PROTAC is to identify an appropriate ligand to bind E3 ligase.
One advantage of PROTAC is that ligand moiety can recruit E3 ligases for mediating degradation even with moderate affinity
The function of PROTAC relies on the expression of the E3 ligase in the corresponding cells,
and the expression level of an E3 ligase in expected and undesired cells influences the efficacy and side effects of PROTAC
The experimental evidence has confirmed that favorable PPIs played a crucial role in the selectivity
and potency of PROTACs and even compensated weak affinity between PROTAC and E3 ligase to assist the formation of ternary complex