Michael Erb

New way to intentionally discover molecular glues could expand drug discovery Scripps Research scientists and colleagues show how drugs that eliminate certain disease-driving proteins can be discovered systematically rather than by chance.

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.

High-throughput ligand diversification to discover chemical inducers of proximity - Nature Chemical Biology Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into mol...

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... 👀

Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules Targeted protein degradation (TPD) is an emergent therapeutic strategy with the potential to circumvent challenges associated with targets unamenable to conventional pharmacological inhibition. Among ...

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.

Does it protect against playoff losses? Go dodgers!

Rewiring DNA repair with PARP-based chemical inducers of proximity 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 ...

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)

Rewiring DNA repair with PARP-based chemical inducers of proximity 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 ...

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...

Efficient genetic code expansion without host genome modifications - Nature Biotechnology Noncanonical amino acids are efficiently incorporated into proteins by optimizing mRNA codon usage.

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...

Yesterday’s game rocked

On my way to #aacr25. I’ll be chairing Part 3 of “Chemistry to the Clinic” tomorrow (4/26 at 2:30) with talks from @dannomura.bsky.social and @xiaoyuzhang.bsky.social. Weather report calls for lots of chemoproteomics, molecular glues, and tough targets. Please join us!

Great news: NIH postbac program is recruiting again! If your grad school plans were affected by program cutbacks or admissions freezes this year I highly encourage you to apply, this could be a perfect opportunity. Please repost.

www.training.nih.gov/research-tra...

Delighted to see our paper finally out in @cp-neuron.bsky.social! Together with Ian MacRae, we developed a new toolbox to study microRNAs and used it to find new mechanisms of Purkinje cell development. Please see the tweetorial from researcher extraordinaire @norjin.bsky.social for details.

Congratulations to Prof. Brian Liau, recipient of this year's Eli Lilly Award in Biological Chemistry, and to the excellent presenters who made up this morning's award symposium!
@michael-erb.bsky.social, Jesus Gutierrez, @brianliau.bsky.social, Yuh Min Chook, @xiaoyuzhang.bsky.social
#ACSSpring2025

excited to celebrate Brian's Eli Lilly award tomorrow and to talk all things molecular glues!

Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules Targeted protein degradation (TPD) is an emergent therapeutic strategy with the potential to circumvent challenges associated with targets unamenable to conventional pharmacological inhibition. Among ...

Happy to share a new preprint from our group in collaboration with AbbVie led by graduate student @inesforrest.bsky.social

www.biorxiv.org/content/10.1...

At his last celebration, he said something that stayed with me: "When you start, you think science is about the papers...then you realize it's about the people."

several of which bat at the top of the order in semester II of Chem Bio here at TSRI

Something that qualifies as big news from my side:
I am very happy and excited to announce that I have been appointed as Life Science Director at AITHYRA, a new Research Institute for Biomedical Artificial Intelligence.

Find out more in the link and 🧵 below

lnkd.in/d_HaGuSE

such exciting news! congrats georg!

Make Thalidomide-for-morning-sickness Great Again

🚨 Chemical Biology & Probes study section (formerly SBCB, one of two NIH panels that reviews chemistry #chemsky 🧪) was abruptly POSTPONED w/no specific plans for rescheduling, less than 24h before start.

If this affects you call your reps & senators, talk to local news, make your voice heard 📢 👩‍🔬

Time stamped right before the USA domination! 😂

Congrats Brian and team. Such an elegant discovery. Small molecules can do it all!

I get that. Obviously I, like Ryan, am at the type of institute that would be among the most severely affected. But I would still like to see good science to get good airtime.

I’m becoming quite good at magical thinking

check out this beautiful science from Xiaoyu, it'll cure your NIH blues for a few minutes

While on clinical service recently, I saw many children who were severely ill due to cancer, flu, and other causes. Sadly this move will mean that healthcare access for many children will be lost, as our institutions suffer from the loss of this critical support:
grants.nih.gov/grants/guide...

Not more dramatic than MJ