Henrik Daub

Abstract Molecular glue degraders (MGDs) are small molecules that co-opt the ubiquitin-proteasome system to induce degradation of target proteins, including those considered undruggable. Their discovery remains challenging due to the lack of rational design strategies and limited throughput of unbiased proteome-wide screening approaches.

Until recently, the discovery of novel targets for targeted protein degradation (TPD) has been largely serendipitous, and the lack of target knowledge was a major bottleneck in the development of small molecule degraders. New technological advances in proteomics and mass spectrometry (MS) show promise in removing this critical hurdle by systematically connecting degrader compounds and their targets, which were previously undruggable.