Ryan Potts - real

LOCKTACs comprise a subset of proximity drugs that stabilize naturally existing complexes. (A) Categories of proximity-based drugs. (B) Mechanism of PROTAC drugs. (C) LOCKTAC acting within a protein-protein interface. (D) LOCKTAC acting adjacent to a protein-protein interface. (E) Heterobifunctional LOCKTAC that does not bind at protein-protein interface. (F) Allosteric drugs induce conformational changes at a distance and are not LOCKTACs.

A new #ScienceReview looks at a different approach to drug discovery that may enable drugging of unconventional targets through stabilization of macromolecular complexes with molecules known as “LOCKTACs.”

Learn more: https://scim.ag/4lC2aCM

LYMTACs:chimeric small molecules repurpose lysosomal membrane proteins for target protein relocalization and degradation Nature Communications - LYMTACs are heterobifunctional small molecules that take advantage of lysosomal membrane proteins to degrade membrane targets via relocalization and lysosomal degradation,...

Check out how the Amgen Induced Proximity team repurpose lysosomal membrane proteins for targeted protein relocalization and degradation using LYMTAC molecules. Now published in @NatureComms. Congrats to @dnalawansha0509.bsky.social and team! #mycompany www.nature.com/articles/s41...

Load and lock: An emerging class of therapeutics that influence macromolecular dissociation Biology is governed by macromolecular interactions, perturbation of which often lies at the heart of disease. Most therapeutic drugs, whether they are small molecules or biologics, exert their effects...

www.science.org/doi/10.1126/...

What if treating disease meant stabilizing biology, not blocking it? We explore that idea in @ScienceMagazine with LOCKTAC molecular glues, a new class of molecules that stabilize natural interactions to either boost or block biology.
science.org/doi/10.1126/sc…shorturl.at/976aj

#mycompnay

Postbaccalaureate Fellow - Research Career Category Research Job Description Join Amgen’s Mission of Serving Patients At Amgen, if you feel like you’re part of something bigger, it’s because you are. Our shared mission—to serve patients...

🎓 Recent STEM grad? Jump-start your PhD journey with Amgen’s new 2-yr paid Postbaccalaureate Research Fellowship in Thousand Oaks! Work with world-class scientists, publish your findings, and make a real impact for patients.
Apply by July 15 ➡️ amgen.wd1.myworkdayjobs.com/Careers/job/...

Our latest paper w/ @pottslab.bsky.social & @amgen.bsky.social in @jacs.acspublications.org by co-first authors @cmzammit.bsky.social & Cory Nadel on discovery of covalent destabilizing degrader of AR & AR-V7 in prostate cancer. Thanks also to @themarkfdn.bsky.social ! pubs.acs.org/doi/10.1021/...

Fabulous! Unfortunately, I’ll have to be there in spirit 👕 this year! Hoping to join at the next world tour 🚌 stop.

SCAM ALERT. This is a fake conference that ripped off my and other people’s names to trick people into registering. There is no such conference that I or the others shown were invited or agreed to. We are working to try to get this fraud taken down from the web.

chemsymposia.com

Now we’re finally talking!

www.politico.com/news/2025/03...

.@pottslab.bsky.social @amgen.bsky.social demonstrate proof-of-concept of disease-specific targeted degradation by redirecting virally encoded E3 ubiquitin ligases with VIPER-TACs. http://dlvr.it/TJgF0r

We anticipate that unbiased phenotypic screening in combination with biased E3-focused small molecule libraries will continue to be a fruitful approach to molecular glue discovery. This amazing work comes from a large team at @amgen.bsky.social in collaboration w/ @PlexiumTx. Congrats to all

SAR analysis provided the opportunity to directly test the impact of altering k-on and k-off rates, which revealed that slow k-off as far more important than fast k-on for degradation activity. 7/8

Comprehensive mutational analysis revealed the GEMIN3 degron by which dGEM3 mediates recognition by VHL. 6/8

We extensively characterize the properties of dGEM3 to show biochemical reconstitution of the VHL:dGEM3:GEMIN3 ternary complex and ubiquitination consistent with a molecular glue without pre-existing affinity between VHL and GEMIN3. 5/7

Proteomics analysis reveals dGEM3 is a highly selective degrader and the direct target is the SMN complex protein GEMIN3. 4/8

We discover dGEM3 as a VHL-based molecular glue causing significant gene expression changes. 3/8

We use an innovative gene expression read out approach to do target-agnostic screening of a focused 26,000 VHL ligand library for molecular glue degraders. 2/8

Discovery of a VHL molecular glue degrader of GEMIN3 by Picowell RNA-seq Targeted protein degradation (TPD) is an emerging therapeutic modality in which small molecules are used to recruit targets to the natural protein degradation machinery of the cell. Molecular glue deg...

🚨 Rational discovery of VHL molecular glues. New Preprint from @amgen.bsky.social Induced Proximity group led by postdoc Jonathan Bushman reports the discovery of a VHL molecular glue degrader of GEMIN3 by Picowell RNA-seq. Read on for details. 🧵1/8 www.biorxiv.org/content/10.1...

Check out this cover highlighting @amgen.bsky.social postdoc Kyle Mangano’s work on VIPER-TACs! 🐍

Thrilled to share the structure of dimerised human PINK1 docked to an endogenous translocase array on the mitochondrial surface, composed of two TOM complexes, bridged by a VDAC2 dimer! Published today in Science www.science.org/doi/10.1126/...

@wehi-research.bsky.social @komanderlab.bsky.social

NIH Grants Fueled $95 Billion In FY 2024 Economic Activity, Finds New Report National Institutes of Health grants generated almost $95 billion in economic activity nationwide in FY 2024 according to a new report by United for Medical Research.

New report shows that NIH grants fueled $95 billion in economic activity and 407,782 jobs in 2024.

That's not to mention the countless lives that biomedical research has saved.

Show me a better investment than that.
www.forbes.com/sites/michae...

Online now! @pottslab.bsky.social @amgen.bsky.social demonstrate proof-of-concept of disease-specific targeted degradation by redirecting virally encoded E3 ubiquitin ligases with VIPER-TACs. http://dlvr.it/TJLmvh

Director of Discovery Proteomics Jobs at Amgen in United States of America Explore the details of a Director of Discovery Proteomics career in South San Francisco. Live. Win. Thrive. Search and apply for a rewarding new career at Amgen.

🚨Hiring Alert🚨 Recruiting an accomplished leader to serve as Director and Head of Discovery #Proteomics at Amgen. Find out more and apply here: careers.amgen.com/en/job/south...

Thanks to all co-authors on this amazing Amgen-UCBerkeley Molecular Therapeutics Initiative collaboration, especially Charlotte Zammit, Cory Nadel, Ying Lin, and Sajjan Koirala. 7/7

Overall, these results indicated that EN1441 is a pathfinding molecule that directly engages AR-v7 Cys125, leading to destabilization and aggregation and the subsequent inhibition of AR transcriptional activity and ultimately ubiquitin-mediated proteasomal degradation. 6/7

Detailed mechanistic studies revealed that EN1441 promotes AR-v7 insolubility leading to aggregation that precedes degradation. 5/7

Further studies revealed that EN1441 inhibits AR-v7 transcriptional activity, leading to gene expression changes consistent with AR pathway inhibition. Importantly, this inhibition is more complete compared to therapies that only inhibit full-length AR and not AR-v7. 4/7

EN1441 directly engages AR-v7 Cys125 and causes proteasome-dependent degradation. 3/7

AR is a heavily drugged target in prostate cancer. A splice variant AR-v7 the occurs during the natural progression of disease has been challenging to drug. We performed a screen for AR-v7 degraders using a covalent fragment library leading to discovery of EN1441. 2/7

Covalent Destabilizing Degrader of AR and AR-V7 in Androgen-Independent Prostate Cancer Cells Androgen-independent prostate cancers, correlated with heightened aggressiveness and poor prognosis, are caused by mutations or deletions in the androgen receptor (AR) or expression of truncated varia...

New @biorxivpreprint.bsky.social preprint from Amgen induced proximity group and @dannomura.bsky.social lab just posted that describes Covalent Destabilizing Degrader of AR and AR-V7 in Androgen-Independent Prostate Cancer Cells. Read on for an overview 1/7 www.biorxiv.org/content/10.1...