4 minute read
May 21, 2023

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

Drug Hunter Team

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.



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