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

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

DOI:
10.3791/59472-v

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10:44 min

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May 15, 2019

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, , , , ,
1Department of Internal Medicine III,University Hospital Ulm, 2Pharmaceutical Institute, Pharmaceutical Chemistry I,University of Bonn

Chapters

  • 00:04Title
  • 00:52Preparation of Proteolysis-targeting Chimera (PROTAC) Homodimer 8 (Compound 8)
  • 04:32Preparation of tert-Butyl N-(1-Methyl-2,6-dioxo-3-piperidyl)carbamate (Building Block 2 for Heterodimer 9)
  • 05:52Functional Validation of PROTAC Compounds
  • 08:12Results: Characterization and Efficacy of PROTACs
  • 09:52Conclusion

Summary

자동 번역

자동 번역

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.

Tags

Keywords: CRBN InhibitionPROTACPomalidomideCereblonE3 Ubiquitin LigaseProtein DegradationChemical SynthesisGlutarimide3-fluorophthalic AnhydrideDiamine Linker

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