Novel Molecular Glue Degraders of P300 & Mechanistic Characterization of Determinants of Selectivity Over Closely Related Paralog CBP
- Monovalent molecular glue degraders for histone acetyltransferase P300 (P300), a high-profile epigenetic target, were identified using Proxygen’s ligaseagnostic screening platform
- Molecular glue induces endogenous p300 degradation and modulates downstream signaling pathways recapitulating genetic dependencies in selected indications
- Ternary complex structural elucidation (Cryo-EM), Molecular Dynamics modeling, combined with biochemical and cellular characterization enabled rational drug design and optimization of preferential degradation of P300 over CREB-binding protein (CBP)