The Targeted Protein Degradation Searchlight network’s launches it’s new Journal Club, where the network delve into the latest research and advancements in the field. In this edition, the network will be focusing on the fascinating realm of molecular glues and their role in targeted protein degradation. Our esteemed moderator, William Farnaby from the University of Dundee, will guide the network through a thought-provoking discussion of three influential papers. These papers shed light on the intricate mechanisms and promising applications of molecular glues. Let’s explore the insights presented in each study.
1. Paper: “An intramolecular bivalent degrader glues an intrinsic BRD4-DCAF16 interaction.”
– Key author: Alessio Ciulli, Centre for Targeted Protein Degradation at The University of Dundee
This preprint highlights the development of an intramolecular bivalent degrader that acts as a glue, facilitating the interaction between BRD4 and DCAF16. This is a preprint only and cannot be shared outside of the network.
2. Paper: “Template-assisted covalent modification of DCAF16 underlies activity of BRD4 molecular glue degraders.”
– Key authors: B. L. Ebert, N. S. Gray, E. S. Fischer
In this preprint, the authors delve into the covalent modification of DCAF16 as a crucial factor in the efficacy of BRD4 molecular glue degraders. This is a preprint only and cannot be shared outside of the network.
3. Paper: “CRISPR Screen Reveals BRD2/4 Molecular Glue-like Degrader via Recruitment of DCAF16.“
– Authors: Andrea G. Shergalis, Violeta L. Marin, David Y. Rhee, Sameera Senaweera, Rebecca L. McCloud, Judith A. Ronau, Charles W. Hutchins, Shaun McLoughlin, Kevin R. Woller, Scott E. Warder, Anil Vasudevan, and Justin M. Reitsma
This study presents a fascinating CRISPR screen that uncovers a BRD2/4 molecular glue-like degrader through the recruitment of DCAF16. By leveraging CRISPR technology, the researchers shed light on the potential of molecular glues in modulating protein-protein interactions and facilitating targeted protein degradation.
What will participants learn?
The goal of the Journal Club is for participants to leave having gained valuable insights into the emerging field of molecular glues and their potential in targeted protein degradation. Through the analysis of these three papers, the network will explore the intricate mechanisms underlying the activity of molecular glues, their design principles, and their implications for therapeutic applications.
We thank William Farnaby for expertly moderating this discussion and shedding light on the significance of these studies. Stay tuned for more enlightening discussions and breakthroughs in the field of targeted protein degradation.