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.