BBB-Permeable PROTACs: Where Do We Stand?

The development of CNS-active PROTACs is limited by the blood–brain barrier (BBB). This Microperspective briefly reviews BBB physiology and critically evaluates current in silico, in vitro, and in vivo models used to assess brain penetration. These considerations enable a unified analysis of the 30 published 30 CNS-targeted degraders compiled here for the first time, highlighting the lack of a consistent design strategy and offering perspectives for future programs.