Crosslinking Profiling of Molecular Glue Degrader-Induced E3 Ligase Interactome to Expand Target Space. (PubMed, Angew Chem Int Ed Engl)
Our approach presents an efficient and robust strategy for identifying neo-substrates recruited to cereblon E3 ligase by the known degraders CC-885 and DKY709, offering valuable insights for clinical evaluation and significantly expanding their target space. Moreover, we developed two novel MG degraders with potent anti-proliferative effects on cancer cells, and application of our method identified neo-substrates, revealing a previously unrecognized target landscape and advancing our understanding of E3 ligase-neo-substrate interactions. Overall, our study provides a powerful tool for neo-substrate identification and expanding target space of E3 ligase, opening new opportunities for developing next-generation MG degraders to address the clinical challenge of undruggable targets.
