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 chemoproteomic strategy reveals how posttranslational modifications reshape protein ligandability across the human proteome, uncovering more than 400 state-dependent interactions, including phosphor...www.nature.com
Excited to share a new preprint from the lab. We show that PTMs like phosphorylation & glycosylation dynamically reshape proteome-wide ligandability in cells, including proteins like KRAS. Great collaboration with the Huang Lab, @forlilab.bsky.social and BMS. www.biorxiv.org/content/10.1...
Post-translational modifications (PTMs) vastly expand the diversity of human proteome, dynamically reshaping protein activity, interactions, and localization in response to environmental, pharmacologi...
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.
At the Bioorganic GRC. Ahmed Bedram just gave a very cool talk on genetic code expansion with quadruplet codons. Check out some of the work here www.nature.com/articles/s41...
Chris Parker
www.biorxiv.org/content/10.1...
Rita Strack
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... 👀
Scripps Research
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.
Craig M. Crews
Brett Garabedian, PhD
pubs.acs.org
Targeted protein degradation (TPD) is an emergent therapeutic strategy with the potential to circumvent challenges associated with targets unamenable to conventional pharmacological inhibition. Among ...
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)
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...
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...
www.biorxiv.org
Chemical inducers of proximity (CIPs) can elicit durable, and often neomorphic, biological effects through the formation of a ternary complex, even at low equilibrium occupancy of their targets. This ...
Scripps Research scientists and colleagues show how drugs that eliminate certain disease-driving proteins can be discovered systematically rather than by chance.
