Repurposing Tolfenamic Acid to Anchor the Uncharacterized Pocket of the PUB Domain for Proteolysis of the Atypical E3 Ligase HOIP

The E3 ligase HOIP is vital for the NF-κB pathway and is implicated in cancer and immunity. However, it remains challenging to achieve high selectivity by directly targeting the conserved catalytic RBR domain of HOIP. Herein, we identified four low-molecular-weight compounds that bind to an uncharacterized pocket of the HOIP PUB domain (HOIP