Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands

Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provid...

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Published in:ACS medicinal chemistry letters 2021-11, Vol.12 (11), p.1733-1738
Main Authors: Bricelj, Aleša, Dora Ng, Yuen Lam, Ferber, Dominic, Kuchta, Robert, Müller, Sina, Monschke, Marius, Wagner, Karl G, Krönke, Jan, Sosič, Izidor, Gütschow, Michael, Steinebach, Christian
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Language:English
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Letter
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Summary:Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provides a blueprint for the assembly of future heterodimeric CRBN-based degraders with tailored properties.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.1c00368