Taming the Beast: How to OptimizeDMPK–PDProperties of Oral Degraders

Expanding the therapeutically relevant biological space represents a valuable alternative to develop safer and more effective medicines via novel modes of action. Compared to the common inhibition methods of protein function, targeting mRNA for degradation upstream in the life cycle of a disease-causing protein offers a novel means to inhibit protein function but also uncovers a new dimension of druggability for challenging hard-to-drug protein targets. Chapter 9 briefly highlights numerous RNA regulatory processes related to mRNA degradation that can potentially be harnessed as therapeutically relevant entry points to affect protein levels. In addition, we showcase the currently available state-of-the-art toolbox that harnesses endogenous cellular RNA quality control pathways for targeted mRNA degradation. Finally, we encourage the research community to embrace mRNA degradation-based modalities in future drug discovery and development campaigns.