Proteolysis targeting chimeras (PROTACs) technology is a novel and promising therapeutic strategy using small molecules to induce ubiquitin-dependent degradation of proteins.
This tutorial review discusses the convergence of drug delivery systems and PROTACs, surveys the burgeoning PROTAC delivery strategies, summarizes their design principles, clarifies their challenges, and outlooks future translational opportunities.
Machine learning (ML) accelerates PROTAC design by optimizing linkers and protein–ligase interactions, enabling selective protein degradation for therapeutic applications, particularly targeting previously undruggable proteins.
A review on current proteolysis targeting chimeras (PROTACs) as chemical probes for histone deacetylase (HDAC) enzymes.
Dual-ligand PROTACs which comprise of two copies of each E3 ligase ligand and targeted protein ligand display superior activity compared to conventional single-ligand PROTACs. The higher activity of dual-ligand PROTACs is enabled by the stabilized and long-lived ternary complex formation.