@pottslab

VP & Head of Induced Proximity Platform, @Amgen | Scientist | Father

 Thousand Oaks, CA
Joined January 2014
  • Tweets768
  • Following368
  • Followers2.2K
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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/scie… #mycompnay

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...

science.org
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A 2025 #ScienceReview looked 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: scim.ag/4lAiKmF #ScienceMagArchives
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AACR
@AACRJul 24
David Puleo, Marina Nelen, Chinatsu Sakata, and Ryan Potts discussed "Degraders in the Era of Precision Oncology" in an #AACRdrugdev26 plenary session chaired by Danette Daniels. @pottslab @danetteldaniels
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Kenneth Loi
@kenjmloiApr 27
Excited to share our discovery of a new programmable RNA-guided DNA-targeting system hiding inside bacteriophages that predates CRISPR. We call it VIPR (Viral Interference Programmable Repeat), and it uses an entirely new logic to find its targets. Thread + link below.
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Apply now to Amgen’s postbacc program! #mycompany
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William Gibson
@wgibsonMar 28
What if a small molecule could activate a transcription factor program in one cell type and destroy the same pathway in another? In our new preprint, we describe one such story on bifunctional molecules that toggle between transactivation and repression.
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Rescuing the Function of Missense-Mutated Tumor Suppressor VHL using Stabilizing Small Molecules biorxiv.org/content/10.64898… #biorxiv_biochem

Rescuing the Function of Missense-Mutated Tumor Suppressor VHL using Stabilizing Small Molecules

Highlights Somatic mutations in the VHL gene, coupled with VHL loss of heterozygosity, drive sporadic clear cell renal cell carcinoma (ccRCC). From structural considerations, we hypothesized that...

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Functional inactivation of the telomerase chaperone TCAB1 primes cells for the activation of ALT in osteosarcoma biorxiv.org/content/10.64898… #biorxiv_cancer

Functional inactivation of the telomerase chaperone TCAB1 primes cells for the activation of ALT in...

Activation of the alternative lengthening of telomeres (ALT) pathway accounts for cellular immortalization in 75% of pediatric osteosarcoma. ALT does not rely on a single enzyme but instead, cataly...

biorxiv.org
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Selinexor is an allosteric degrader: it stabilizes XPO1/CRM1 to expose a cryptic ASB8 E3 ligase site, triggering ubiquitination. Led by Casey Wing, Joyce Fung & Bert Kwanten. #TargetedDegradation #Allostery nature.com/articles/s41589-0…
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Mapping the latent CRBN-molecular glue degrader interactome biorxiv.org/content/10.64898… #biorxiv_molbio

Mapping the latent CRBN-molecular glue degrader interactome

Molecular glue degraders (MGDs) are a transformative modality in drug discovery. MGDs that work in concert with the E3 ligase CRL4CRBN can degrade a range of substrates through tailored MGDs. To...

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Orthosteric Molecular Glue Inhibits COP9 Signalosome with Substrate-Dependent Potency biorxiv.org/content/10.1101/… #biorxiv_molbio

Orthosteric Molecular Glue Inhibits COP9 Signalosome with Substrate-Dependent Potency

Orthosteric inhibitors block enzyme active sites and prevent substrates from binding. Enhancing their specificity through substrate dependence seems inherently unlikely, as their mechanism hinges on...

biorxiv.org
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Kaiyi Jiang
@idmjky20 Sep 2025
Thrilled to share that I have joined @Amgen as the inaugural Amgen Science Fellow. I look forward to partnering with colleagues to design next-gen therapeutic by integrating AI/ML with high throughput synthetic biology platforms. linkedin.com/posts/drhoward-…

#mycompany | Howard Chang

At Amgen, we believe that delivering for patients requires us to explore bold ideas and develop new scientific approaches. I’m especially proud to highlight the work of our inaugural Amgen Science...

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Itai Yanai
@ItaiYanai7 Sep 2025
Legend David Baltimore died yesterday. He understood the way things should work: "the real contribution of @MIT is that it doesn't take itself too seriously. It takes ideas seriously, but the people are relatively informal. They are not self-aggrandizing the way academics can be.
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KaelinLab@kaelin_lab28 Aug 2025
Thrilled to share our work to find natural products that inhibit β-catenin! This is the result of an amazing collaboration with @theNCI Natural Products Branch and shows the power of 'up' assays to find new and interesting molecules! biorxiv.org/content/10.1101/…

Positive Selection Screen for Natural Product β-Catenin Inactivators

Cell-based phenotypic screening of natural product mixtures can reveal new biological and pharmacological principles but has been largely abandoned, partly because such mixtures can be difficult to...

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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: scim.ag/4lAiKmF
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.

ALT 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.

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Great to see our two in-house developed kinetic stabilizers, Tolcapone and PITB, against transthyretin amyloidoses cited as examples of an emerging therapeutic class: LOCKTACS. science.org/doi/10.1126/scie…

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...

science.org
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Talking of @amgen they also have cool LYMTACs: chimeric small molecules repurpose lysosomal membrane proteins for target protein relocalization & degradation nature.com/articles/s41467-0…

LYMTACs:chimeric small molecules repurpose lysosomal membrane proteins for target protein relocal...

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

nature.com
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Degradation without E3s? Cool approach here - molecules that drag membrane proteins into lysosomes for degradation Might help get around KRASi resistance
Ryan Potts@pottslab10 Sep 2024
🚨New @biorxivpreprint from the @Amgen Induced Proximity group. Here we introduce LYMTACs: Chimeric Small Molecules Repurpose Lysosomal Membrane Proteins for Target Protein Relocalization and Degradation. 🧵 biorxiv.org/content/10.1101/…

LYMTACs: Chimeric Small Molecules Repurpose Lysosomal Membrane Proteins for Target Protein Reloca...

Proximity-inducing modalities that co-opt cellular pathways offer new opportunities to regulate oncogenic drivers. Inspired by the success of proximity-based chimeras in both intracellular and...

biorxiv.org
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Amgen’s LOCKTAC molecular glues are changing how we target disease. 🔬 AMG 193, now in clinical trials, is designed to lock PRMT5 to MTA in MTAP-deleted tumors. Read more about how Amgen is working to innovate in this space.

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Check out how we repurpose lysosomal membrane proteins for targeted protein relocalization and degradation using LYMTAC molecules. Now published in @NatureComms. Congrats to @nalawansha and team! #mycompany nature.com/articles/s41467-0…
Ryan Potts@pottslab10 Sep 2024
🚨New @biorxivpreprint from the @Amgen Induced Proximity group. Here we introduce LYMTACs: Chimeric Small Molecules Repurpose Lysosomal Membrane Proteins for Target Protein Relocalization and Degradation. 🧵 biorxiv.org/content/10.1101/…

LYMTACs: Chimeric Small Molecules Repurpose Lysosomal Membrane Proteins for Target Protein Reloca...

Proximity-inducing modalities that co-opt cellular pathways offer new opportunities to regulate oncogenic drivers. Inspired by the success of proximity-based chimeras in both intracellular and...

biorxiv.org
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