ZL-216

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional mols. that consist of a protein of interest (POI) ligand, an E3.Ubiquitin ligase (E3) ligand, and an optimized linker to attach both ligands.1 Upon binding to a POI, PROTACs induce proximity of the POI and E3.Result in the formation of a productive "POI-PROTACs-E3" ternary complex,which facilitates the ubiquitination and subsequent degradation of. The POI via the ubiquitin-proteasome system. In the past two decades, PROTACs have advanced.Dramatically and evolved from peptidebased PROTACs and small-mol.PROTACs to orally efficacious clin. candidates that degrade pathogenic proteins.In patients.2 In this issue of Mol. Therapy Nucleic Acids, Zhang et al. successfully developed a novel PROTAC that employed.Nucleic acid aptamer instead of a peptide or small mol. as the POI ligand.3 According to this design principle, they reported.The first nucleolin-targeting aptamer-constructed PROTAC ZL216, which selectively degraded nucleolin in vitro and in vivo.They also showed that ZL216 could inhibit the proliferation and migration of hormone.