A Reliable and Sustainable Multicomponent Access to Protein Degraders

The use of small molecules to induce targeted protein degradation is increasingly growing in the drug discovery landscape and protein degraders have progressed rapidly through the pipelines. Despite the advances made so far, their synthesis still represents a significant burden and new approaches are urgently demanded. Herein, we report an unprecedented platform that leverages the modular nature of both multicomponent reactions and degraders to enable the preparation of highly decorated PROTACs and hydrophobic tag-mediated degraders. Compared to the existing methods, our approach offers a versatile and cost-effective means to access libraries of protein degraders and increase the chance of identifying successful clinical candidates.