Molecular Glues: From Mechanisms to Therapeutics

Molecular glue (MG) degraders represent an exciting new modality in drug discovery highlighted by their ability to degrade undruggable targets and their favorable pharmacological properties. Thus far, only a very small number of MG degraders have been serendipitously found, most of which act on CULLIN4 E3 ubiquitin ligases. The scarcity of these novel compounds limits our understanding of their activity requirement, E3 ligases preference, and functional versatility, thereby hindering the prospective discovery of new MG degraders. In this presentation, I will highlight our latest studies on the identification of new MG degrader compounds as well as human disease mutations acting as genetic glues that foster neo-substrate-E3 interactions. These findings point to potential rational strategy for rational discovery of target-centric MG degraders.

Speaker: Ning Zheng, University of Washington