Therapeutic Antibodies: Bench to Market

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The current predominant therapeutic paradigm is based on maximizing drug-receptor occupancy to achieve clinical benefit. This strategy, however, generally requires excessive drug concentrations to ensure sufficient occupancy and efficacy, often contributing to adverse side effects. The proteolysis targeting chimeras (PROTACs) method uses bi-functional molecules to recruit ubiquitin E3 ligases to a specific protein target of interest, catalytically inducing its ubiquitination and degradation, therefore providing efficacy that is not limited by equilibrium occupancy. In addition, PROTACs also allow targeting non-enzymatic scaffolding function and potentially long-acting effect. As the number of E3 ligases amenable to recruitment continues to grow, PROTAC induced-protein degradation represents a new pharmacological strategy for highly efficient chemical protein knockdown with utility both as a chemical biology tool and also potentially as a clinically useful therapeutic modality.

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