The transition from bivalent to trivalent degraders might not immediately seem like an obvious approach for improvement of degradation outcomes, particularly given the chemical synthesis challenges and presupposition that increasing molecular weight of degraders would be accompanied by lack of cellular permeability or poor pharmacokinetics. However, with the trivalent PROTAC studied here, we have demonstrated that this is not the case. While indeed SIM1 has slightly reduced permeability compared to parent bivalent inhibitor and PROTACs, it outperformed those in relevant cellular assays used for assessment of BET compound potential for therapeutic use. Furthermore, the remarkably favourable PK profile of SIM1 suggests trivalent PROTACs will be appropriate for in vivo use despite their increased molecular weight.