Scaffold hopping enables direct access to more potent PROTACs with <i>in vivo</i> activity
George M. Burslem, Daniel P. Bondeson, Craig M. Crews
Abstract
Herein we employ a scaffold hopping approach to enhance the activity of a previously reported BCR-Abl PROTAC. This represents a significant advance in the PROTAC field since it can abrogate the need to optimize the linker to access a more potent degrader. The new PROTAC demonstrates a >10 fold increase in ability to induce degradation and demonstrates in vivo activity.
Topics & Concepts
ScaffoldIn vivoChemistryScaffold proteinNanotechnologyMaterials scienceEngineeringBiomedical engineeringBiologySignal transductionBiochemistryBiotechnologyProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysMultiple Myeloma Research and Treatments