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Updated: Dec 18, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Scaffold hopping enables direct access to more potent PROTACs with in vivo activity
George M Burslem1, Daniel P Bondeson1, Craig M Crews2
1Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA. Craig.Crews@Yale.edu.
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.
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