Happy to share the final version of this work is now out in @natchembio.nature.com. Lots of additional exciting data! Congrats to all the authors!
A @natchembio.nature.com study led by Assoc. Prof. @michael-erb.bsky.social describes a strategy to deliberately discover “molecular glue” degraders by converting existing protein binders into compounds that recruit the cell’s disposal machinery, selectively degrading ENL and BRD4.
What a thrill to see this out! Our prospective, scalable, and target-centric solution for molecular glue discovery.
More thoughts and details here: www.linkedin.com/posts/activi...
Paper here: www.nature.com/articles/s41...
Dear friends and colleagues,
I am excited to share a preprint describing my take on extracellular targeted protein degradation (eTPD) - a proximity modality termed Sheddase-Targeting Chimeras (SHEDTACs).
www.biorxiv.org/content/10.6... 👀
Happy to share the final version of this work out in ACS CS. Inspired by ‘binding-focused’ chemoproteomic methods, we developed a ‘function-focused’ strategy to agnostically identify degradable proteins.
This was a big team effort led by
@inesforrest.bsky.social
and in collaboration with AbbVie.
www.biorxiv.org/content/10.1...
One detail we are very excited about: the potential for PCIPs to selectively target tumors with acquired resistance to conventional PARP inhibitors. while KO of PARP1 is a major mechanism of resistance to PARPi, PARP1 knockout cells are actually more sensitive to PCIP-1. (3/3)
Thanks to @durocher1.bsky.social & all collaborators. Highlights: a generalizable strategy to discover new classes of CIPs, synthetic lethality with BRCA mutations, overcoming resistance to conventional PARP inhibitors, and proof-of-concept for rewiring DNA repair with proximity pharmacology. (2/3)
New work out today introducing PCIPs, heterobifunctional chemical inducers of proximity that inhibit DNA repair by recruiting BET proteins to PARP2. Great work uncovering a new form of event-driven pharmacology by Bryce/Eric/Erin and the rest of the team. (1/3)
www.biorxiv.org/content/10.1...