Approaches for targeted protein degradation: From biology to drug development

Targeted protein degradation is a new therapy approach that is quickly gaining traction. Proteins are destroyed selectively by the cell’s endogenous ubiquitin-proteasome system. The formation of a ternary complex between the protein to be degraded, an E3 ligase that carries out ubiquitinylation of the targeted protein, and a molecule that links the protein to be degraded and the E3 ligase, such as proteolysis targeting chimeras (Protacs) or molecular glues, initiates targeted protein degradation. Compared to well-established therapeutic principles such as target protein inhibition, targeted protein degradation provides a fundamentally different strategy. This special issue presents developments and problems in targeted protein degraders across fields such as biology, chemistry, and pharmaceutical development. The special issue on targeted protein degradation aims to collect a diverse range of research on the subject, including those relevant to molecular and structural biology, medicinal chemistry, and pharmaceutical development.