@SevLechner

Postdoc in Winter lab, CeMM. Rewiring transcription factors — chemical proteomics — target deconvolution — drug discovery

 Wien, Österreich
winter-lab.com
Joined April 2020
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Using a chemoproteomic competition assay, we previously identified MBLAC2 as off-target of more than 20/50 profiled HDAC inhibitors (nature.com/articles/s41589-0…)

Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target

Nature Chemical Biology - Lechner et al. used an affinity-based chemical proteomics approach to investigate the target landscape of HDAC inhibitors, and identified an extracellular vesicle...

nature.com
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We characterized HINT1 and NME1-4 inhibition with enzyme activity assays, molecular docking, and co-crystal structures.
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Key takeaways: a) every second HDAC inhibitor with a phenylhydroxamic warhead inhibits MBLAC2 b) NME1-4 and HINT1 are now targetable with small molecule inhibitors c) chemoproteomics is always good for surprises 🙂
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Paper alert! We report the first inhibitors for nucleoside kinases NME1-4 and for the nucleotide-binding protein HINT1. On top, we provide probes for MBLAC2, an off-target of every second (!) hydroxamic acid-based HDAC inhibitor! tinyurl.com/yh92vh6b 👇🧵

Serendipitous and Systematic Chemoproteomic Discovery of MBLAC2, HINT1, and NME1‑4 Inhibitors from...

Abstract. Metalloenzyme inhibitors often incorporate a hydroxamic acid moiety to bind the bivalent metal ion cofactor within the enzyme’s active site. Rece

pubs.acs.org
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Proteome-wide measurements of dose–response curves for 144 drugs reveal drug mechanisms of action go.nature.com/4a9lMs8 rdcu.be/egMl1

Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomics

Nature Biotechnology - Proteome-wide measurements of dose–response curves for 144 drugs reveal drug mechanisms of action.

nature.com
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You can now also find me on bluesky @SevLechner.bsky.social
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🏆 Congrats to @georg_e_winter for receiving an @ERC_Research Consolidator Grant for GE|NEomorph, a project reprogramming cancer cells via transcription factors. It opens new avenues for targeted therapies in the fight against #cancer #ERCCoG ➡️ Read more: bit.ly/41h3AMG
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Finally! It is happening! After 6 years of hard work by formidable teams in 13 institutions @RESOLUTE_IMI, we have ordered and validated the results and are able to share the FOUR (4) papers aimed at assigning functional properties to each human SLC #membranetransporter
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You have a strong background in bioinformatics🖥️, data science📈, machine learning, and multi omics? You want to do a PhD👩‍🎓facilitating non-clinical safety assessment? If so, come and join our ProteomicsDB team. mls.ls.tum.de/compms/job-off…
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Proud to see our 'detective story' on uncovering the MoA of Orpinolide published in its final form in @nchembio! Immensely grateful to @georg_e_winter, the Waldmann lab @mpimoph and @laraialab for being part of this fantastic collaboration!
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Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomics go.nature.com/4a9lMs8
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We are happy to announce that decryptE is out, another step towards better understanding of drug MoAs. 🎉After elucidating the target space of drugs and how they dose-dependently alter PTMs in cells (decryptM),... (1/4)
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...and another new Preprint coming right on its heels! This time by Jakob Trendel and colleagues. doi.org/10.1101/2024.04.04.5…
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🔬 Research teams led by @georg_e_winter (CeMM) & @alessiociulli (University of Dundee) have found a new system that triggers cellular waste disposal. Published in @Nature, the findings shed light on mechanisms & therapeutic opportunities of this system ➡️ bit.ly/3Pejn8b
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Are you a final year international PhD student or PDRA considering opportunities in Chemical Biology in London? Please contact me - the EDV group is on the look for prospective candidates for a Newton Fellowship application to tackle protein phosphatases edv-lab.com/join-us/

Join us!

The EDV group is looking for a prospective medicinal chemist to join the team for an exciting PhD project funded by AZ-EPSRC Industrial Doctoral Landscape Award. Find more information on the projec…

edv-lab.com
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Me referring to a 'recent paper' in my writing and realise that 2017 was in fact 6 years ago
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Telos, as they say. Love the consideration of HDAC6 in cardiovascular disease. This deal brings me back to postdoc days in Schreiberia. Cut my teeth as a chemical biologist on HDAC6 with @SchreiberStuart, learning so much from @mazit. Degraders of HDAC6 could be even more interesting... endpts.com/novartis-licenses…
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