Excited to share the newest discovery and BioRxiv preprint from our Novartis-Berkeley Center for Proteomics and Chemistry Technologies on the development of a new induced proximity-based therapeutic modality: Deubiquitinase Targeting Chimera (DUBTAC) platform for Targeted Protein Stabilization. Congrats to first author UC Berkeley chemical biology graduate student Nathaniel Henning, as well as co-authors Lydia Boike, Jessica Spradlin, Carl Ward, Bridget Belcher as well as Novartis Institutes for BioMedical Research team Scott Brittain, Matt Hesse, Dustin Dovala, Lynn McGregor, Jeff McKenna, John Tallarico, and Markus Schirle. And thanks for support from The Mark Foundation for Cancer Research!

In this study, we disclose a covalent recruiter EN523 against the K48 ubiquitin chain-specific deubiquitinase OTUB1 that targets an allosteric cysteine C23. We show proof-of-concept of targeted protein stabilization by making a heterobifunctional DUBTAC linking EN523 to the mutant CFTR targeting drug lumacaftor and show robust stabilization of mutant CFTR protein in human bronchial epithelial cells.