Alessio Ciulli

Induced ubiquitination of the partially disordered Estrogen Receptor alpha protein via a 14-3-3-directed molecular glue-based PROTAC design Proteins lacking defined ligandable pockets remain challenging drug targets. Here, we develop a molecular glue-based PROTAC (MGPROTACs) approach that chemically conjugates a molecular glue stabilizer ...

Exciting @biorxivpreprint.bsky.social by the groups of @pjcossar.bsky.social and @alessiociulli.bsky.social. They use a molecular glue between 14-3-3 and an intrinsically disordered domain of ERα to develop a molecular glue-based PROTAC recruiting VHL. doi.org/10.1101/2025...
#TPD #ChemSky #ChemBio

An absolute pleasure to work with all co-authors on this study: from @alessiociulli.bsky.social’s lab (the 🤝 House of VHL 🤝) @alesalerno.bsky.social & Gajanan Sathe – and our wonderful collaboration Graham Marsh and Hannah Maple from Tocris Bio-Techne

@alessiociulli.bsky.social we are looking forward to your presentation at our #UbiquitinFunction meeting in Portugal ☀️ Please share this with your followers to let them know you will speaking, and to register & submit today to join us!
bit.ly/47DJnU2

Great to see you Julien!

Get ready for the PROTACS, targeting proteins related to cancer and potentially other diseases
a new feature @nature.com
www.nature.com/articles/d41...

Targeted protein degradation for cancer therapy Nature Reviews Cancer, Published online: 25 April 2025; doi:10.1038/s41568-025-00817-8Targeted protein degradation (TPD) is an emerging pharmacological modality in cancer therapy. In this Review, Hinterndorfer et al. outline the mechanistic bases of TPD and discuss the characteristics, advantages and applications of established compounds as well as upcoming classes of degraders.

NEW content online!

Incredibly grateful and thankful for the resilience and brilliance of my postdocs @mariarrios.bsky.social and Conner Craigon, the incredible support by @b45her71.bsky.social and Mark Nakasone, and the talented team at Tocris led by Hannah Maple. Brilliant team-science!

We love it as it works real well! We are curious to hear your thoughts and learn feedback as you try it out for your own research, so do reach out we are happy to share all reagents and ahead of the key products becoming available via Tocris @biotechne.bsky.social

Excited to share our latest preprint introducing BromoCatch - our cool new Tag solution for protein self-labeling inside cell. This should be a useful addition to the current arsenal of tools eg Halo, Snap. Link to the paper to catch your attention! => www.biorxiv.org/content/10.1...

Thank you Biochemical Society it is an honour on behalf of all of the team present and past member to receive this award. Everyone at @dundeeuni.bsky.social and @boehringerglobal.bsky.social are very proud of this recognition of our model reimagining how academia and industry work together

Delighted to see this, many congratulations and fully deserved! The Boehringer foundation and your colleagues are lucky to have your vision leading this initiative. I am excited as our collaboration will thrive in your new home, and by opportunities for AITHYRA and CeTPD to work together in future

Something that qualifies as big news from my side:
I am very happy and excited to announce that I have been appointed as Life Science Director at AITHYRA, a new Research Institute for Biomedical Artificial Intelligence.

Find out more in the link and 🧵 below

lnkd.in/d_HaGuSE

Well done @holmqvist89.bsky.social and @nurkocaturk.bsky.social - dream team! ;)

Check-out the first paper from @farnabygroup.bsky.social developing novel chemistry for plate-based PROTAC assembly that in a single Direct-to-Biology (D2B) screen delivers a potent hit that degrades the target protein in the brain of a mouse. Delighted to see this out and kudos to all co-authors

Congratulations to our Keystone Proximity-Based Therapeutics conference travel scholarship winners Christine Ng @stanford-chemh.bsky.social and @alesalerno.bsky.social at CeTPD Dundee! @keystonesymposia.bsky.social

Congratulations to @alesalerno.bsky.social from University of Dundee CeTPD and Christine Ng from @stanford-chemh.bsky.social who have been selected as recipients of our conference travel scholarships to attend the Proximity-based Therapeutics Keystone conference @keystonesymposia.bsky.social!

Go Ale go! 💪👍🙏

Nice work team!

Our privilege to coauthor a paper with the inimitable @giuliosupertifurga.bsky.social and his amazing team! Thank you 🙏 Giulio for the great collaboration and Kudos to Gernot in GSF Lab and Conner and Diane in my Lab and to all the coauthors. Macrocyclic PROTAC chemistry by @yutingcao.bsky.social

Collaboration with @supertifurgalab.bsky.social out in @cp-cellchembiol.bsky.social we identify a role of ABCC1 transporter in PROTAC efflux. It turns out, getting in is surprisingly not often the problem; it’s keeping it once inside the cell! Maybe some wider lessons. Designing it out could be key

The best way to start 2025: New Year, New Paper! Happy to see (finally!) the science of Amphista therapeutics coming out on @biorxivpreprint.bsky.social Work led by @andre-head.bsky.social and Scott Hughes and congrats to the entire Amphista team involved on the drug development and mode of action.

It was such a fun experience exploring the endless possibilities that unconventional ideas (and chemotypes!) can bring to life! 💡 Huge kudos to everyone who was part of this exciting project! 💫🧪

Cool to learn you like it! 👍

Loads! The idea first emerged ~7y ago at a group meeting, @andre-head.bsky.social recalls well. He was keen but had his hands full. 4 years later until anyone took the suggestion seriously (Claudia) she had many plates spinning too but @alesalerno.bsky.social had just joined and really run with it!

Ternary Complex-Directed Dynamic Combinatorial Chemistry Enables Discovery of Potent VHL Homo-PROTACs Dynamic combinatorial chemistry (DCC) leverages a reversible reaction to generate compound libraries from constituting building blocks under thermodynamic control. The position of this equilibrium can...

Last Christmas, Claudia and Alessandra gave us DCC PROTACs doi.org/10.26434/che... .. This year, to keep us in the theme, they together with Lianne are giving us something special.. 🎶 Big kudos to them all and great job @alesalerno.bsky.social for championing this. Let us know your thoughts! 5/5

Our findings, supported by NMR conformational analyses, reveal ferrocene’s ability to act as a versatile and effective dynamic linker in PROTACs. This opens up new avenues for designing next-gen chemical tools and starting points for therapeutics with optimised molecular dynamics. 🌟 4/5

Compared to benchmark PROTACs from 3 different classes, not just BETs (!) but also VHL and CRBN degraders, FerroTACs achieved:
✅Intramolecular interactions that foster a folded state in non-polar environments
✅Robust target degradation
✅Improved cell permeability
✅Reduced efflux liabilities
3/5

We integrated in the linker ferrocene—an organometallic structure with freely rotating cyclopentadienyl rings around a sandwiched iron metal ion. This unique “molecular hinge” introduces dynamic flexibility and chameleonicity to PROTACs. ⚙️✨ 2/5

🚨 Exciting News! 🚨

What happens when unconventional ideas drive to push boundaries? 🚀 Meet FerroTACs: a novel #PROTAC design using ferrocene as core unit to re-imagining linker design and fine-tune their phys-chem properties. Learn more about our work led by @alesalerno.bsky.social here: 🧪👇 1/5

Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2 - Nature Communications SH2 domains are challenging to target using small molecules. Here, the authors develop phosphotyrosine-based covalent ligands of the E3 ligase SOCS2 using structure-based design. A pro-drug approach y...

Great work by group members @dyylaanl.bsky.social TomWebb and Beth Forrester. Our SOCS inhibitor is described in @naturecomms.bsky.social here=> doi.org/10.1038/s414...; chemical probe info in EUbOpen portal www.eubopen.org/sites/www.eu...