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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Article DOI: 10.3791/59472-v • 10:44 min • May 15th, 2019
May 15th, 2019 •
*1, *2, 1, 2, 2, 1
1Department of Internal Medicine III, University Hospital Ulm, 2Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn
* These authors contributed equally

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This work describes the synthesis and characterization of a pomalidomide-based, bifunctional homo-PROTAC as a novel approach to induce ubiquitination and degradation of the E3 ubiquitin ligase cereblon (CRBN), the target of thalidomide analogs.

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Chemical Inactivation E3 Ubiquitin Ligase Cereblon Pomalidomide-based Homo-PROTACs Molecular Mechanism Thalidomide Analogs Physiological Function Protein Degradation CRBN Inhibition Anti-tumor Activity Clinical Implications Obesity Infectious Diseases Disorders Synthesis Linkers Attachment Protein Degraders Designing A PROTAC Compound Boc-protected L-glutamine Tetrahydrofuran Round-bottomed Flask 1,1'-carbonyldiimidazole 4-pyridine Reflux Glutarimide Compound Ethyl Acetate Separatory Funnel Deionized Water Brine Sodium Sulfate
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