POI (Protein of Interest) refers to the target protein, namely the disease-causing protein or key functional protein that undergoes degradation or functional modulation in molecular glue-mediated processes. The Molecular Glue POI Library consists of a series of fragments that can specifically bind to different types of POIs. As key components of molecular glues, these ligands form stable interactions with target proteins, laying the foundation for molecular glues to induce the interaction between POIs and E3 ubiquitin ligases. The covered POIs include various types such as cancer-associated GSPT1, androgen receptors, and abnormally aggregated proteins linked to neurodegenerative diseases.

This fragment library can be applied to the screening and optimization of targeted protein degraders. By screening ligands with high affinity and strong selectivity for specific POIs from the library, core structures can be identified to develop novel molecular glues. For instance, optimization of ligands targeting GSPT1 has yielded molecular glue degraders with enhanced degradation activity. Since many POIs are difficult to drug due to the lack of traditional small-molecule binding pockets, some ligands in the POI Ligand Library can modulate such POIs by inducing protein-protein interactions, thereby further expanding the scope of drug discovery for undruggable targets.

MCE has compiled a POI Fragment Library comprising thousands of POI fragments with molecular weights ranging from 150 to 400. This compound library can be widely applied in Molecular Glue research and development.