Excited to highlight our latest bioRxiv led by grad student Zoe Duong and Qian Shao. We report a chemistry-centric, chemoproteomics-enabled strategy to discover non-degradative molecular glues for transcriptional rewiring.
🔗 www.biorxiv.org/content/10.6...

Discovery of Non-Degradative Covalent Molecular Glues for Transcriptional Reprogramming

Transcriptional reprogramming through induced proximity has emerged as a powerful strategy for modulating the expression of oncogenic and tumor-suppressive genes. Inspired by transcriptional reprogram...

biorxiv.org

New preprint out! We show that PROTAC-induced ubiquitination can bypass canonical ERAD to degrade ER membrane proteins. Wonderful collaboration w/ @dannomura.bsky.social and huge credit to grad student superstar Sydney Tomlinson! www.biorxiv.org/content/10.1...

Induced ubiquitination bypasses canonical ERAD to drive ER protein degradation

Heterobifunctional proteolysis-targeting chimeras (PROTACs) have emerged as a powerful strategy to degrade disease-relevant proteins, enabling targeting of previously "undruggable" proteins. Current d...

biorxiv.org

I rarely get to give a research talk at my home institution! Looking forward to giving a talk about our latest research next Tuesday, November 18th, at 2 pm as part of the @innovativegenomics.bsky.social seminar series in Room 115 IGIB at UC Berkeley! innovativegenomics.org/events/semin...

Reimagining Druggability using Chemoproteomic Platforms

Reimagining Druggability using Chemoproteomic Platforms - Innovative Genomics Institute (IGI)

innovativegenomics.org

Induced proximity-based therapeutic modalities nature.com/articles/s41... rdcu.be/eOfBH This new Review by @dannomura.bsky.social et al. discusses the rapidly expanding landscape of therapeutic approaches based on inducing proximity between proteins, including targeted protein degraders and more

Induced proximity-based therapeutic modalities - Nature Reviews Drug Discovery

Induced proximity modalities encompass monovalent and bifunctional agents, such as molecular glues and proteolysis-targeting chimeras, that induce an interaction between biomolecules to functionally m...

nature.com

New from the Cravatt Lab! Tryptoline stereoprobes reveal hidden cysteine ligandability: while Boltz-2 nails orthosteric sites but burns out on non-orthosteric ones. A masterpiece of chemoproteomics + AI. 🔗 doi.org/10.1101/2025...

Tryptoline Stereoprobe Elaboration Identifies Inhibitors of the GRPEL1-HSPA9 Chaperone Complex

Activity-based protein profiling has identified hundreds of proteins from diverse classes that react at specific cysteine residues with stereochemically defined electrophilic compounds (stereoprobes) ...

doi.org

We unveil TRACERs, Transcriptional Regulation via Active Control of Epigenetic Reprogramming: a new small-molecule-based induced-proximity modality that silences transcription factors by recruiting endogenous corepressor complexes for locus-specific repression. www.biorxiv.org/content/10.1...

Targeted Transcriptional Repression by Induced Proximity

Most cancer driving proteins remain undruggable due to the absence of ligandable pockets and their reliance on intrinsically disordered or protein-DNA/protein-protein interactions. Transcription facto...

biorxiv.org

Looking forward to seeing friends and giving a talk about our latest research at @stanfordchemistry.bsky.social @stanforduniversity.bsky.social tomorrow! chemistry.stanford.edu/events/chemi...

Chemical Biology Seminar: Professor Dan Nomura, University of California, Berkeley | Chemistry

About the Seminar "Reimagining Druggability using Chemoproteomic Platforms"The Nomura Research Group is focused on reimagining druggability using chemoproteomic platforms to develop transformative med...

chemistry.stanford.edu

We’re happy to highlight our newest @biorxivpreprint.bsky.social by postdoc Thang Cong Do and Octant on the discovery of a direct-acting, covalent destabilizing degrader of immune & cancer transcription factors IRF8 & IRF5! Also thanks to @themarkfdn.bsky.social ! www.biorxiv.org/content/10.1...

Covalent Degraders of Immune Regulatory Transcription Factors IRF8 and IRF5

Transcription factors are among the most challenging targets for drug discovery due to their lack of classical binding pockets and high degree of intrinsic disorder, despite the therapeutic importance...

biorxiv.org

This paper now out in ACS Central Science!! pubs.acs.org/doi/10.1021/...

DCAF16-Based Covalent Degradative Handles for the Modular Design of Degraders

While targeted protein degradation is a powerful strategy for eliminating disease-causing proteins, the rational design of monovalent or molecular glue degraders remains challenging. In this study, we...

pubs.acs.org

Dan Nomura@dannomura.bsky.social · last yr.

Excited to highlight our latest preprint by graduate student Lauren Orr on the discovery of a covalent degradative handle that acts through two unique C173 and C178, on the E3 ligase DCAF16 that can be used to modularly design monovalent and bifunctional degraders. www.biorxiv.org/content/10.1...

Awesome to be back in Cambridge for #ChemBiointhePub ahead of the Bioorganic Chemistry GRC!

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/...

Excited to announce a new collaboration between the Molecular Therapeutics Initiative (MTI) and Amgen Inc.! This partnership includes funding for cutting-edge research & an internship program for grad students to train in drug discovery & development at Amgen. #MTI #Amgen #Biotech #UCB

Bioorganic GRC is set! I got tired of the lack of swag so made a couple of unofficial tees. Order one if you want to support the conference (or simply enjoy strange looks in grocery stores). Spirit: chembio-shop.fourthwall.com/products/grc... World Tour: chembio-shop.fourthwall.com/products/spi...

Spirit

Preliminary score: ND

chembio-shop.fourthwall.com

Thrilled this paper is out! We solved the first cocrystal structure of FSP1 with an inhibitor (FSEN1), providing mechanistic insight & a foundation for medchem. Led by Amalia Megarioti & Sitao Zhang. A terrific collaboration with Da Jia. Brief Skytorial! 1/9

Cocrystal structure reveals the mechanism of FSP1 inhibition by FSEN1 | PNAS

FSP1 is an FAD-dependent oxidoreductase that uses NAD(P)H to regenerate the reduced forms of lipophilic quinone antioxidants, such as coenzyme Q10 ...

pnas.org

Congrats to chem bio grad students Ellie King, Lauren Orr, and Vienna Thomas on graduating with their PhD's!

Our 2025 lab photo!

- Mutations mimicking glues by @brianliau.bsky.social al and Ning Zheng - Covalent and bivalent glue engagement by @dannomura.bsky.social, Nathanael Gray, @georgwinter.bsky.social and @alessiociulli.bsky.social - And finish it of with a discussion on general mode-of-action.

Excited that our work revealing the structure and function of the monster stress response silencing factor, the E3 ligase SIFI, is now out! Congratulations to the most amazing team of Zhi Yang, Diane Haakonsen, Michael Heider and Sam Witus! www.nature.com/articles/s41...

www.statnews.com/2025/05/06/h...

How to stop the shift of drug discovery from the U.S. to China

U.S. pharmaceutical companies are increasingly licensing new drugs from China. Former FDA Commissioner Scott Gottlieb explains how to stop the shift.

statnews.com

New-preprint alert! We use chemoproteomic profiling to show MYST KAT inhibitors exhibit hierarchical target engagement (KAT6A/B > KAT7 >> KAT8). Reminiscent of Type I kinase inhibitors, the selectivity of these small molecules varies based on concentration. www.biorxiv.org/content/10.1...

Excited to highlight our latest preprint by graduate student Lauren Orr on the discovery of a covalent degradative handle that acts through two unique C173 and C178, on the E3 ligase DCAF16 that can be used to modularly design monovalent and bifunctional degraders. www.biorxiv.org/content/10.1...

DCAF16-Based Covalent Degradative Handles for the Modular Design of Degraders

Targeted protein degradation (TPD) is a powerful strategy for targeting and eliminating disease-causing proteins. While heterobifunctional Proteolysis-Targeting Chimeras (PROTACs) are more modular, th...

biorxiv.org

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!

Excited to moderate a panel at the @theaacr.bsky.social CICR townhall at #2025AACR on "Charting the Course: Innovating Cancer Drug Discovery in a Challenging Landscape" alongside Shiva Malek, Gwenn Hansen, Ryan Schoenfeld, and Joseph Pearlberg!

Back in Chicago for #2025AACR! I’ll be giving a talk on our latest work tomorrow in the Educational Session on Advances in Ligand Discovery to Enable Previously Intractable Targets on Sat Apr 26th 2:30-4:00pm in S406 McCormick South alongside @michael-erb.bsky.social & @xiaoyuzhang.bsky.social !

Amazing talk yesterday by @rushika-perera.bsky.social for our Molecular Therapeutics seminar series!

Had such an awesome time at @themarkfdn.bsky.social symposium today!!

The Mark Foundation for Cancer Research@themarkfdn.bsky.social · last yr.

Great afternoon of talks by @dannomura.bsky.social, Jeff Rathmell, Jun Wang, and Cathy Wu on reimagining druggability, the impact of obesity on immunotherapy response, antigen presentation inhibitors, & neoantigen discovery. That’s a wrap on #MarkSymposium 2025 – thanks for following along!

Amazing Quality Control Life Processes conference in Frankfurt organized by @idikic.bsky.social !! Great science, great friends!

Cool paper from Woo lab: https://www.biorxiv.org/content/10.1101/2025.03.24.645050v1

Cool paper from Rullo lab: www.nature.com/articles/s41...

Mimicry of molecular glues using dual covalent chimeras - Nature Communications

The authors report the development of dual covalent proximity inducing molecules capable of selectively cross-linking two non-interacting proteins. Through the selective proximity-based activation of ...

nature.com

Cool paper from Crabtree and Gray labs: www.biorxiv.org/content/10.1...

A Bivalent Molecular Glue Linking Lysine Acetyltransferases to Oncogene-induced Cell Death

Developing cancer therapies that induce robust death of the malignant cell is critical to prevent relapse. Highly effective strategies, such as immunotherapy, exemplify this observation. Here we provi...

biorxiv.org