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.
Targeting chimeras (TACs), such as PROTACs, LYTACs, AUTACs, and ATTECs, has emerged as a promising strategy for selectively degrading proteins. The linker of the TACs plays a critical role in determining the spatial arrangement, stabilizing the ternary complex, and determining degradation efficiency.
ATP-Competitive inhibitors do not inhibit a kinase's non-catalytic, scaffolding roles. Instead, this goal may be accomplished by targeted protein degradation.