We wondered whether PROTAC degradation activity could be improved by increasing their cell permeability. To this end, it is worth keeping in mind that requirements on cellular permeability are relaxed because, unlike inhibitors, PROTACs do not have to fully occupy the target binding site for the duration of their action. Indeed, the catalytic mode of action of PROTAC degraders via formation of stable ternary complex can compensate for low membrane permeability, as we have shown for the archetypical BET degrader MZ1. However, optimal ternary complexes are often challenging to achieve without the "trial and error" approach involving the synthesis and testing of many compounds. Thus, we aimed to develop a set of simple parameters for optimization which could be applied during initial compound design or to existing PROTACs in order to improve bioactivity through increased membrane permeability.