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BBB-Permeable PROTACs: Where Do We Stand?
Serena Francisco1, Giulia Apprato1, Matteo Rossi Sebastiano1
1Department of Molecular Biotechnology and Health Sciences, MedChemBeyond Lab, University of Torino, Piazza Nizza 44bis, 10126 Torino, Italy.
None:
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.
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