- Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands.
Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands.
ACS medicinal chemistry letters (2021-11-20)
Aleša Bricelj, Yuen Lam Dora Ng, Dominic Ferber, Robert Kuchta, Sina Müller, Marius Monschke, Karl G Wagner, Jan Krönke, Izidor Sosič, Michael Gütschow, Christian Steinebach
PMID34795861
ABSTRAKT
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.
MATERIAŁY