Dual-ligand PROTACS mediate superior target protein degradation <i>in vitro</i> and therapeutic efficacy <i>in vivo</i>
Yong Chen, Zihan Xia, Ujjwal Suwal, Pekka Rappu, Jyrki Heino, Olivier De Wever, Bruno G. De Geest
Abstract
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.
Topics & Concepts
In vivoIn vitroLigand (biochemistry)Dual (grammatical number)ChemistryDegradation (telecommunications)Cell biologyPharmacologyBiophysicsBiochemistryBiologyReceptorComputer scienceBiotechnologyTelecommunicationsArtLiteratureProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysPeptidase Inhibition and Analysis