Degrader Radar, Apr. '23: DCAF1, on CNS Degraders, and More

This article highlights six recent articles of interest in the field of targeted protein degradation including but not limited to potentially new ligases, recruiting motifs, and a discussion on the feasibility of CNS-penetrant degraders.

1. “Reinstating targeted protein degradation with DCAF1 PROTACs in CRBN PROTAC resistant settings”

Novartis, Basel, CH + Cambridge, MA
BioRxiv, April 14, 2023

This Novartis study identified a novel non-covalent ligand for the E3 ligase receptor DCAF1 for use in targeted protein degradation and developed several proof-of-concept PROTACs including a potent and selective DCAF1-BTK PROTAC (DBt-10) that can overcome resistance to CRBN-based degradation. These findings highlight the versatility of DCAF1 for TPD and offer a new avenue for developing therapies for diseases where catalytic inhibition is not an option.