Targeting the degradation of proteins involved in neuroblastoma with bivalent ligands.

Recent innovations in the field of targeted protein degradation via manipulation of the ubiquitin-proteasome system open up new therapeutic possibilities for disorders that cannot be targeted with conventional inhibitor paradigms. In this project we aim to synthesize new bivalent ligands and evaluate/optimize these to tune the post-translational degradation of protein targets involved in neuroblastoma. To maximize the chance of identifying PROTAC (proteolysis targeted chimeras) hits, we will use our toolbox of diverse and versatile PROTAC reagents, which may be swiftly coupled to a small molecule ligand of the target to be degraded. We have established an academic collaboration to gain access to state-of-the-art cellular and in vivo models for neuroblastoma, which are indispensable for the evaluation and optimization of the PROTACs.