Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems
June 2026
in “
Acta Pharmacologica Sinica
”
TLDR Improving PROTAC delivery systems can enhance their effectiveness and speed up their use in medicine.
Proteolysis-targeting chimeras (PROTACs) face challenges in clinical translation due to their "beyond-rule-of-five" physicochemical properties, which affect bioavailability and distribution. This review highlights chemistry-driven strategies to improve PROTAC delivery, focusing on innovations in prodrug and linker engineering for precise control and release. Delivery vehicles like lipid-based, polymeric, and inorganic nanoscaffolds, along with antibody and aptamer conjugates, offer platforms for targeted delivery. The integration of medicinal chemistry with delivery science aims to optimize selectivity, uptake, and therapeutic windows, potentially accelerating PROTACs' clinical application by enhancing their pharmacokinetic properties and degradation efficacy.
