Some bonus #SummerReading from our #DrugDiscovery project EUbOPEN in @natcomms.nature.com - this is linked to the work on NUDT5 we wrote about last year at link.europa.eu/cPWFVY #HorizonEU

ChemBioHub - Huber Lab@chembiohub.bsky.social · 2d ago

1/ The toolkit behind the discovery is out. In @natcomms.nature.com, we report the selective NUDT5 degrader toolkit that helped uncover NUDT5’s hidden biology - and show antagonistic roles for NUDT5 and NUDT15 in 6-TG response. doi.org/10.1038/s414...

🧬𝗡𝗲𝘄 𝗶𝗻𝘀𝗶𝗴𝗵𝘁𝘀 𝗶𝗻𝘁𝗼 𝗮 𝗱𝗲𝗰𝗮𝗱𝗲𝘀-𝗼𝗹𝗱 𝗹𝗲𝘂𝗸𝗲𝗺𝗶𝗮 𝗱𝗿𝘂𝗴 Stefan Kubicek's group at #CeMM & the Huber lab (@chembiohub.bsky.social at @ox.ac.uk) show that NUDT5 regulates the response to the #leukemia drug 6-TG through its physical presence in the cell. 🔗 bit.ly/4z0a3tt 📄 @natcomms.nature.com: bit.ly/4q9yQYb

1/ The toolkit behind the discovery is out. In @natcomms.nature.com, we report the selective NUDT5 degrader toolkit that helped uncover NUDT5’s hidden biology - and show antagonistic roles for NUDT5 and NUDT15 in 6-TG response. doi.org/10.1038/s414...

Targeted Protein Degradation of NUDT5 Dissociates Catalytic Inhibition from Protein Loss in 6-Thioguanine Response - Nature Communications

Thiopurines are widely used drugs whose activity depends on cellular metabolism. Here, the authors develop chemical tools to remove NUDT5 and show that protein loss, but not inhibition, alters drug re...

doi.org

🧬 Scientists from IMI project EUbOPEN have worked out how an enzyme called NUDT5 acts as a handbrake on the production of a building block of DNA. The finding, published in @science.org, explains why some cancers are resistant to treatment. 👉 link.europa.eu/cPWFVY #HorizonEU @chembiohub.bsky.social

New in @natcomms.nature.com: a live-cell BRET biosensor to study how PRMT5 inhibitors engage their target in a tumour-context cellular environment (1/4) Open access paper: doi.org/10.1038/s414...

A BRET biosensor for measuring uncompetitive engagement of PRMT5 complexes in cells - Nature Communications

This study presents a BRET biosensor that measures how anticancer drugs cooperatively engage PRMT5 complexes in cells, revealing how cellular metabolites such as SAM and MTA enhance drug action and en...

doi.org

www.ox.ac.uk/news/2025-11... @ox.ac.uk @medsci.ox.ac.uk

Discovery reveals ‘handbrake’ that controls cancer drug response |

Oxford University and Austrian researchers uncover a previously unknown ‘handbrake’ mechanism controlling how cells respond to cancer drugs, reshaping global understanding of cell metabolism and drug

ox.ac.uk

Here's the beautiful paper from @chembiohub.bsky.social reporting NUDT5's role in purine synthesis. I cannot emphasize enough how gracious and open these authors were when we all realized we were working on the same mechanism.

ChemBioHub - Huber Lab@chembiohub.bsky.social · 9mo ago

New in @science.org 🧬 What if an enzyme you thought you knew turned out to control metabolism in a completely new way? We found that NUDT5 acts as a molecular handbrake on purine synthesis, reshaping how cells make DNA building blocks and respond to cancer drugs. www.science.org/doi/10.1126/...

Beautiful discovery by the Huber and Kubicek labs and a wonderful example of using targeted protein degradation to probe novel non-catalytic functions.

ChemBioHub - Huber Lab@chembiohub.bsky.social · 9mo ago

New in @science.org 🧬 What if an enzyme you thought you knew turned out to control metabolism in a completely new way? We found that NUDT5 acts as a molecular handbrake on purine synthesis, reshaping how cells make DNA building blocks and respond to cancer drugs. www.science.org/doi/10.1126/...

1/New paper from Zheng Wu, Phong Nguyen et al. @cri-utsw.bsky.social shows how cells balance the two pathways that produce purine nucleotides: de novo purine biosynthesis (DNPB) and purine salvage. The surprising mechanism involves NUDT5, a Nudix hydrolase www.science.org/doi/10.1126/...

NUDT5 regulates purine metabolism and thiopurine sensitivity by interacting with PPAT

Cells generate purine nucleotides through de novo purine biosynthesis (DNPB) and purine salvage. Purine salvage represses DNPB to prevent excessive purine nucleotide synthesis through mechanisms that ...

science.org

17/NUDT5 is having a moment – see excellent work from other labs reporting roles for NUDT5 in purine metabolism. These include papers by Kilian Huber and Stefan Kubicek, also out today (see link), and work by Alexis Jourdain and Jun Yang (see next posts) www.science.org/doi/10.1126/...

A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis

Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...

science.org

New in @science.org 🧬 What if an enzyme you thought you knew turned out to control metabolism in a completely new way? We found that NUDT5 acts as a molecular handbrake on purine synthesis, reshaping how cells make DNA building blocks and respond to cancer drugs. www.science.org/doi/10.1126/...

A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis

Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...

science.org

If you have defended your PhD in Biochemistry or a related field in 2023 or have a publication in this field in 2023 (PhD less than 4 years ago), consider applying for the Förderpreis of the @gdchbiochem.bsky.social of @gdch.bsky.social. Deadline: April 30th. en.gdch.de/network-stru...

Awards & Honors | Gesellschaft Deutscher Chemiker e.V.

en.gdch.de

Jensen Huang’s comments from JPM24 are now summarized in a Nvidia blog post. He doubles down on exactly the kinds of things that I’ve been cautioning are wildly optimistic. More below. 👇🏽 1/

We have two postdoc positions available for structural biologists to help us study the function of proteins involved in RNA & ubiquitin metabolism. Deadline 9th October 2023. Links: 1) tinyurl.com/msc4vckb 2) tinyurl.com/4dukkuy6

Excited to inaugurate our Bluesky account with this paper from our friends in the Tan lab on a matrix-augmented pooling strategy for thermal profiling - glad we could contribute! www.sciencedirect.com/science/arti...

Target deconvolution with matrix-augmented pooling strategy reveals cell-specific drug-protein inter...

Target deconvolution is a crucial but costly and time-consuming task that hinders large-scale profiling for drug discovery. We present a matrix-augmen…

sciencedirect.com

Hello Bluesky! Please tell us why you had to hide away for sooo long!