Figure 1.

The concept of the four pillars of translational pharmacology is applied to PROTACs. First, the PROTAC has to get access to its site of action. Next, it must bind to both the target protein as well as the targeted E3 ligase to form a ternary complex. That ternary complex must then mark the target protein for degradation by the proteasome. Finally, degradation of the target protein together with inhibition of what activity remains must translate to the relevant downstream effect.