Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands.
Aleša BriceljYuen Lam Dora NgDominic FerberRobert KuchtaSina MüllerMarius MonschkeKarl G WagnerJan KrönkeGobec Izidor SosičMichael GütschowChristian SteinebachPublished in: ACS medicinal chemistry letters (2021)
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.