Thrilled to share that, together with my colleagues
@UoDCeTPD
and collaborators
@Boehringer
, we report
@ScienceMagazine
the breakthrough discovery and characterization of a small-molecule that degrades most oncogenic mutant forms of KRAS. 1/8
Excited to debut XL01126 – a first-in-class PROTAC degrader for the protein kinase LRRK2, a high-profile target in Parkinson’s disease. Great
#CeTPD
collaboration with Dario Alessi
@mrcppu
team and
@RuiMoreira_UL
Please share, thread below
Excited to share our latest work describing MN714 – first-in-class covalent inhibitor of SOCS2, a substrate adaptor of Cul5 E3 ligase. A >5-years long journey in the making full of twists and surprises. Please Retweet! Thread below 1/13
Honoured and humbled to receiving the prestigious Prous award. It recognises our group’s work over >10years on VHL PROTACs. It could not have been possible without the dedication and contributions of so many students, coworkers and collaborators and funders support. Thank you all
And congratulations to
@alessiociulli
for winning the EFMC Prous Institute -Overton & Meyer award 2022 for new technologies in drug discovery
#EFMCISMC22
I have decided to shut down all our group’s Labs activities by the end of this week. I am no longer comfortable with an official line of "business as usual". The time has come to act responsibly and come together into this.
#SocialDistancing
#FlattenTheCurve
#WorkFromHome
Introducing Trivalent PROTACs: where cooperativity and avidity of binding go hand-in-hand to boost targeted protein degradation outcomes. Great collaboration with Danette Daniels group
@promega
Pre-print just out now - Let us know what you think!
It’s hard to keep track of the protein degradation literature as it grows stronger day-by-day. Our
#TPD
journal club aims to provide a platform to help you stay on top of it! Here’s the latest Issue (August), Eds: Angus and Sarath. Hope you like it!
21 years ago I came to study in the UK because of the
#Erasmus
programme. It changed my life and was instrumental in my decision to return to do a PhD. It is sad and disappointing to learn that future generations will miss out from an opportunity, because of this decision.
Excited to debut our latest work where Dynamic Combinatorial Chemistry (DCC) meets bifunctional molecules (PROTACs). We have just posted our pre-print in
@ChemRxiv
@chemRxivBiochem
Feedback welcome, and here’s a thread 🧵 👇 1/9
We've updated our DCAF16-BRD4 preprint with lot new data: structure-design picomolar degraders, glues to a distinct E3 ligase (DCAF11) and revised title: Targeted protein degradation via intramolecular bivalent glues
@UoDCeTPD
@ollie_lh
@georg_e_winter
Happy to contribute with a review covering von Hippel-Lindau (VHL) ligands and PROTACs in the themed collection on induced proximity modalities in
@ChemSocRev
Great work
@CJ_Diehl
#OpenAccess
=>
Cheers 🍻 to exactly 11 years of the group in Dundee
@UoDLifeSciences
@dundeeuni
A great evening out marking a big milestone, now within our exciting new
@UoDCeTPD
!
Excited to introduce CRBN-Midi: a construct engineered to accelerate biophysics and high-resolution crystallography of CRBN ligands and degraders design. A tour-de-force work at
@UoDCeTPD
by a fantastic team led by Alena Kroupova and David Zollman. 1/11
Thrilled to watch our trivalent PROTAC work finally out. So incredible journey from concept to practice, and again awesome collaboration with the amazing Kristin and
@danetteldaniels
@promega
There’s a curious backdrop story on how it all started, keep reading below 👇🏼
New work from
@alessiociulli
@danetteldaniels
and coworkers reports trivalent PROTACs targeting two domains in the same protein that enhance protein degradation via increased avidity and cooperativity. Free to read:
Huge congratulations to
@AmphistaThera
on the grand-opening of their new research site at GrantaPark in Cambridge. Delighted to be able to join Nicki and team and connect with new ppl and friends to celebrate 🎊 🎉 a very feel good day!
PLease RT! We have 4x opening at postdoctoral level to join our new
@CeTPD_Dundee
. Covering all range of disciplines, both academic in
@farnaby84
team and in our drug-discovery teams
@Boehringer
and
@AlmirallUS
. DM for informal enquiries
Check out our news story piece in
@NatureNV
on LYTACs: protein degraders that go extracellular. Congratulations to
@CarolynBertozzi
@StevenMBanik
and coworkers on this beautiful work!
Transmembrane and extracellular proteins can be targeted for degradation by a new class of potential drug molecules - read all about it in this great N&V by Claire Whitworth and
@alessiociulli
Our pan-KRAS PROTAC degrader ACBI3 is now live and available to order on
@Boehringer
#OpnMe
portal. Thanks to the team for making this available to scientists for free so quickly after the release of our
@ScienceMagazine
publication!
We plan to make ACBI-3 freely available for the community through the
#OpnMe
portal, no strings attached. We welcome feedback on this study, and hope ACBI-3 will prove invaluable in accelerating further research on this important cancer target. 6/8
Very happy our work on improving VHL ligands is now out
@ACSBioMed
#jmedchem
great teamwork with Michael Gutschow and co. at Bonn. We design a new di-Methyl analogue of VH101 (cmpnd 30) and qualify it as the most potent VHL inhibitor in vitro and in cell
Nicole Trainor and I have offered a beginner’s guide to PROTACs and targeted protein degradation, now out in
@The_Biochemist
. We hope this will prove useful to the community, from degradation newbies to practitioners!
Super-proud of this work by
@CharlCrowe
and the entire team! It has been my dream since starting working on PROTACs >15 years ago to one day see them working in action, glued to their Cullin RING ligase and target protein. It is dream come true now! Beautiful and Thank you 🙏
Mechanistic and structural insights into degrader-targeted protein ubiquitinability, now out in
@ScienceAdvances
!
Let's make more degraders that hit the bull's eye 🎯
@alessiociulli
@UoDCeTPD
Completion of our
@dundeeuni
spin-off new-co Amphista therapeutics’s Series A investment announced today! Great news and congratulations to the whole team for this achievement. Read more here and below /1
Excited to debut XL01126 – a first-in-class PROTAC degrader for the protein kinase LRRK2, a high-profile target in Parkinson’s disease. Great
#CeTPD
collaboration with Dario Alessi
@mrcppu
team and
@RuiMoreira_UL
Please share, thread below
It has been a privilege to contribute to the prestigious
@AnnualReviews
of Biochemistry. It’s special times to work on E3 ligases, and this piece by Angus and I attempts to capture some of the emerging interactions and concepts.
#TPD
#PROTACs
#glues
Outstanding talk by Brian Lanman
@Amgen
on the discovery of first-in-class KRAS G12C covalent inhibitor Sotorasib. A fantastic tour de force of structure-based drug design
Excited and humble to be part of team KOODAC to innovate degraders of undruggable tumour drivers as molecular therapeutics for pediatric cancers funded by
@CancerGrand
We’re assembling a strong team in our group at
@UoDCeTPD
Reach out if you’re interested in joining the effort
We’re excited to reveal that team KOODAC, which includes
@alessiociulli
of
@UoDCeTPD
, has been selected by
@CancerGrand
to receive up to $25m to take on one of cancer’s toughest challenges.
Learn more 👉
So thrilled to witness structural and mechanistic insights coming out from us at
@UoDCeTPD
@UoDLifeSciences
and from Brenda Schulman
@MPI_Biochem
and Gary Kleiger
@UNLV_CoS
! Prime time for seeing the entire Cullin RING Ligase machines in actions on targets glued by our degraders!
Excited to share our structural snapshots of MZ1-targeted Brd4BD2 ubiquitination in
@biorxivpreprint
!
@alessiociulli
@UoDCeTPD
We use cryo-EM to capture states of the dynamic Brd4BD2-MZ1-(NEDD8)-CRL2VHL-UBE2R-Ub complex
🔗
We keep sharing our best and most-validated reagents with the community to advance research! Happy to see our construct designed for E.coli expression of recombinant CRBN-Midi protein now available via
@Addgene
to advance CRBN TPD research. 1/3
Thrilled to announce the lineup of speakers and open applications for our symposium to mark the opening of
@UoDCeTPD
! It promises to be a wonderful occasion to celebrate our field. Having so much fun to work in this with
@val_spiteri
@CharlCrowe
@CraigMCrews
Brenda and team!
We're thrilled to announce our line up of confirmed speakers for our Symposium in May 2024! We invite you to apply via the link below. We hope you are as excited as we are for 3 days of science and Scottish fun!
Apply->
We all want to glue our targets, but how? Here, we describe a new strategy to achieve just that: bridging across to an adjacent site to anchor an intrinsic E3 ligase interaction. Fantastic work
@ollie_lh
Matthias Angus Ken
@TasukuIshida1
@georg_e_winter
and all involved
In our recent paper with
@alessiociulli
we unravel a novel modality of targeted protein degradation: Intramolecular gluing of protein domains to generate a target-E3 ligase interaction surface. Live now on Biorxiv:
Humble and proud of receiving this
@CR_Horizons
award on behalf of everyone at
@UoDCeTPD
@UoDLifeSciences
and
@Boehringer
who’s made this collaboration possible and contributed to the scientific innovation from the team! In London with Kirsten, Stephanie, Aileen, and
@VesnaVetma
Structures of the Cul5 ligase SOCS2 bound to EpoR and GHR reveals the structural basis of E3-substrate recognition - and ushers development of new E3 ligands as handles for targeted protein degradation
#PROTACs
. Paper just out in
@NatureComms
Please RT: We are looking for postdoctoral scientists to join and boost our efforts in protein degradation
#TPD
#PROTACs
. Feel free to get in touch for informal enquiries - position 1/2
Fantastic to host
@D_B_McConnell
and many of our
@Boehringer
colleagues and collaborators in Dundee
@UoDCeTPD
to celebrate the success of our continued partnership. Together since 2016 to innovate PROTAC drug discovery.
Do you want to ride the wave of
#PROTAC
#degraders
? I am building a new drug discovery team within my group
@UoDLifeSciences
in collaboration with
@AlmirallUS
, recruiting 1x team leader + 4x scientists. Do get in touch for informal enquiries:
Many congratulations
@CarolynBertozzi
and the other awardees. A much deserved recognition to their important and impactful work developing and applying chemistry to probe biology. A feel-good day for chemical biology, for sure!
BREAKING NEWS:
The Royal Swedish Academy of Sciences has decided to award the 2022
#NobelPrize
in Chemistry to Carolyn R. Bertozzi, Morten Meldal and K. Barry Sharpless “for the development of click chemistry and bioorthogonal chemistry.”
Amid current WFH we’ve launched a monthly Journal Club covering
#PROTAC
and
#TPD
literature amongst others! Spearheaded by Siying, we are pleased to share our first Issue, edited by Siying and
@farnaby84
Please RT and let us know what you think:
The Dundee-Vienna axis strengthens! Our first
#CeMM
-
#CeTPD
collaboration paper with
@georg_e_winter
Group illuminate on the emergence and mechanism of E3 Ligase missense mutations to protein degraders. Great 🧵on the main findings 👇🏼
Happy to introduce a fantastic collaboration with
@alessiociulli
& team. We integrated functional genomics & structural bio to identify functional hotspots in hijacked E3s and found them mutated in patients relapsing from degraders 🧵👇
Two institutions with a tradition for innovation and a common vision can create something special when they come together. Proud of our fantastic joint PROTAC drug discovery team who are making the dream come true!
@dundeeuni
@UoDLifeSciences
@Boehringer
@D_B_McConnell
Interested in developing degrader drugs that could save lives of kids with cancer? Look no further. We are recruiting 4 scientists at
@UoDCeTPD
to do just that as part of our
@CancerGrand
#CancerGrandChallenges
KOODAC team. Role 1/4: Senior Lead Scientist
Excited and humble to be part of team KOODAC to innovate degraders of undruggable tumour drivers as molecular therapeutics for pediatric cancers funded by
@CancerGrand
We’re assembling a strong team in our group at
@UoDCeTPD
Reach out if you’re interested in joining the effort
So excited to be with my graduate student Tom Webb at Keystone Colorado for this conference. We had a great day skiing yesterday- a perfect prelude to what promises a fantastic 3-days of science. Come chat (and ski ⛷️) with us!
@KeystoneSymp
#KSProteinDeg24
#KSProximityTx24
Check our latest review on bispecific small molecules that bring proteins together, including
#PROTACs
- just out in Curr Opin Chem Biol with
@chiaramaniaci
Our amide-to-ester subsitution paper is finally out now in J Med Chem!
Big thank you to co-first author
@ToriKleinPhD
, to Conner Craigon and to
@alessiociulli
and Scott Lokey for helping to put together this cool story!
#TPD
#medchem
#PROTACs
Wanna join a dynamic group of dedicated creative
#TPD
researchers and be part of an exciting new venture? Dundee’s Centre for Targeted Protein Degradation (CeTPD) is opening new roles and it could be for you! Feel free to reach out for informal enquiries
So excited for our
#CeTPDnewhome
Four years in the making, and it is finally happening! Fantastic team-work planning and executing such a big move, even if just across the road!
@UoDLifeSciences
Team CeTPD has officially moved into our new home. Here’s a video of us settling into our new offices and labs. Despite moving hundreds of boxes, it’s been such a good week of team bonding! Can’t wait to get sciencing!🎉🎉
@alessiociulli
@farnaby84
@UoDLifeSciences
I am very excited to announce that our new
@UoDCeTPD
is now on Twitter! Please RT / Follow us! We look forward to share the latest from our Centre and to engage with the wider community and outreach across the globe about our work on TPD, glues, induced proximity and beyond.
We are delighted to officially launch our Twitter channel.
Follow us to keep up to date with the Centre - our research, activity, and opportunities to work with us.
Follow us on
@LinkedIn
as well:
#TargetedProteinDegradation
#PROTACS
International Potluck dinner at
@UoDCeTPD
starting now! Fast becoming a tradition! Kudos to
@val_spiteri
for organizing and everyone for cooking their favorite dishes! 😋.
SH2 domains thought of as "undruggable" - A News & Views by Oliver Hantschel highlights recent work from
@alessiociulli
lab
@NatureComms
on an inhibitor of the SH2 domain of E3 ligase SOCS2. Read it here and the original article
Love these concise and highly informative med chem posts on newly disclosed drug structures. Great community service
@drughuntersite
@HartungIngo
et al.
Excited to take part in this event and share some of our work on
#PROTACs
#TPD
and discuss current and future directions in the field with colleagues and friends
@georg_e_winter
Danette Daniels
@promega
Klemens Hoegenauer
@Novartis
and many others
Do not forget our 6th EFMC-YSN MedChemBioOnline on PROTAC and Small Molecules Development
📆January 28 (17:00 to 19:15 CET)
More information & registration:
The event is free and open to all thanks to the generous support of Symeres
cc
@YoungSciNet
Please RT: Postdoc position available immediately in my group to investigate the structure, mechanism and druggability of new E3 ubiquitin ligases using structural cell biology.
@UoDLifeSciences
@DundeeUniJobs
@mrcppu
Excited to share our latest review in
@COSB_CRSB
We take a snapshot on current solution-based structural biology methods and studies of ternary complexes formed by PROTACs and molecular glues, and offer a forward-looking perspective of where the field may go next
Our review on the scope of using in solution sturctural biology techniques to study ternary complexes is now live! We have a lot of fun preparing this piece, with plenty of debates at the pub!
@KevinHaubrich1
@alessiociulli
@farnaby84
@FrankSobott
Pleased to see this story now out
@ASBMB
@jbiolchem
@srochaliv
@juliantyfrost
: Von Hippel-Lindau (VHL) small molecule inhibitor binding increases stability and intracellular levels of VHL protein
Exciting science by amazing scientists and teams, and so well deserved recognition on some truly groundbreaking work on what my favourite molecules of life, proteins, look like. Congratulations!
BREAKING NEWS
The Royal Swedish Academy of Sciences has decided to award the 2024
#NobelPrize
in Chemistry with one half to David Baker “for computational protein design” and the other half jointly to Demis Hassabis and John M. Jumper “for protein structure prediction.”
Chemical Biologists: Interested in starting a group working on protein phosphorylation or ubiquitination? Here’s a great opportunity to join
@dundeeuni
@UoDLifeSciences
@mrcppu
👇🏼
🔥🔥🔥 Registrations open for the
#BarcelonaBiomed
Conference "Proximity-inducing Pharmacology: Targeted Protein Degradation & Beyond"! 22-24 May
#TPD
#chembio
@IRBBarcelona
NO registration fee: run!!!🏃♀️🏃♀️
Short talks & posters
An amazing lineup of speakers & chairs😍
👇👇
Very excited to see our
#CRBN
-midi article which we first preprinted last January 👇🏼now published in
@NatureComms
Kudos to Alena, David and the whole multidisciplinary team at
@UoDCeTPD
@UoDLifeSciences
Excited to introduce CRBN-Midi: a construct engineered to accelerate biophysics and high-resolution crystallography of CRBN ligands and degraders design. A tour-de-force work at
@UoDCeTPD
by a fantastic team led by Alena Kroupova and David Zollman. 1/11
Excited to see this finally out: SMARCA2 isoform-selective (90% identical bromodomain sequence) and orally bioavailable PROTAC degrader ACBI2 achieves efficacy in SMARCA4-deficient tumour models in vivo. Great teamwork
@UoDLifeSciences
#CeTPD
@Boehringer
@farnaby84
@ChemHaWei
Ever wanted to dephosphorylate just a single phosphoprotein instead of blocking all downstream kinase substrates with a kinase inhibitor? Check our new PoC paper describing PhosTACs that recruit phosphatases to selected phosphoproteins.
#PhosTACs
We continue to open our probes to the community!
@Boehringer
now provides free access to our dual Brd7/9 PROTAC degrader VZ185 (and the inactive negative control) on The compound was discovered by Vittoria Zoppi
@sjz_hughes
@chiaramaniaci
@EndriuT
Today we announce a new partnership with
@biotechne
to commercialise technology developed here at the University that enhances the understanding of undruggable diseases.
Read more about this exciting project 👉
So proud of this study by
@martina_pierri
and
@xingui_liu
beginning to unveil how subtleties in PROTAC “linkerology” can impact the key steps of the mode of action in unpredictable ways. Ft. our signature Xray-ITC combo by Zoe and Alena, and chem-magic by
@alex_hallatt
@UoDCeTPD
So happy to see this paper out! In this work we present how a single stereochemical inversion within a PROTAC linker impacted conformational rigidity and binding mode. A special thanks to
@alessiociulli
and all
#CeTPD
members!
Check out our Dundee-BI team work to develop ACBI-2, an orally bioavailable VHL-based PROTAC that selectively degrades SMARCA2 (Brm) over SMARCA4 (Brg1) and shows TGI in mouse xenographs models of lung cancer in vivo
Very excited! And super proud of the amazing teamwork within our Local Organizing Committee making this all possible and helping to bring the best flavours of our hometown Dundee to the world of TPD
#TPDfocus
@UoDCeTPD
We have 300 goodie bags packed and ready to go for our delegates!
@alessiociulli
is clearly very excited about his new reusable shopping bag! Big thanks to the CeTPDers who helped pack these!
New PK data on OpnMe portal qualifies the Smarca2/4 (Brg1/Brm) degrader ACBI1 as appropriate for in vivo studies. Sharing this data enables the field to make best use of the compound
#openaccess
@Boehringer
@UoDLifeSciences
Thought of PHD fingers as undruggable reader domains? Our fragment screening work, just out in ACS
@ChemicalBiology
, suggests otherwise: they are - at least - ligandable!
Over the moon as Amphista therapeutics snaps this Year’s Scrip Award! So proud of the A-team led by Nicki and Ian, what an amazing achievement!
@EndriuT
@sjz_hughes
you rock!
Excited to launch the start of a new collaboration on
#TPD
#PROTACs
between
@UoDLifeSciences
and the Barcelona-based pharmaceutical company Almirall. Check this space - more to follow soon as we build the team !
The University is to partner with global biopharmaceutical company Almirall to develop new treatments for severe skin diseases with high level of unmet medical need
@UoDLifeSciences
@alessiociulli
@UoDRIS
A positive of the 2020 Lab shutdown is that we got to write more reviews than we would have done otherwise. Here are three so far: 1) Synthetic and medicinal chemistry of phosphotyrosine analogues, with
@n_makukhin
in
@rsc_medchem
/1
We invite you to save the date! We will be hosting”Protein Degradation in Focus, a special symposium to celebrate the opening of CeTPD in Dundee” on 19-22 May 2024. Scientific co-organisers,
@alessiociulli
, Brenda Schulman,
@CraigMCrews
,
@val_spiteri
&
@CharlCrowe
!
I am in deep shock, still. Huib was a wonderful scientist and colleague and fun to talk science with at conferences. This is how I like to remember him.
Good-news Friday! With our newly announced Dundee’s Centre for Targeted Protein Degradation and Dundee’s TPD spin-off Amphista therapeutics we feel happy to contribute to and proud to be a part of our thriving innovating community
@dundeeuni
@UoDLifeSciences
The power of collaboration: Congrats to Scott Lokey
@ucsc
and Lokey Lab grad-student Tori Klein on their work on 'Understanding and Improving the Membrane Permeability of VH032-Based PROTACs' now published in
@ACSMedChemLett
It was fun and a pleasure to do this little interview with
@ThatsTVScotland
on behalf of all our colleagues and collaborators
@UoDCeTPD
@CeMM_News
briefly explaining our “protein sandwich” recently published at
@Nature
- thanks for the opportunity.
"We called it like a protein sandwich."
@alessiociulli
from
@UoDCeTPD
has led research into defining a new class of molecular glue which could significantly enhance cancer and neurodegenerative disease treatments.
Happy to see the “Next Generation Therapeutics” Section of Curr Opin Chem Biol finally out. It has been a pleasure to share and co-edit with Ingrid Wertz
@bmsnews
. Check our Editorial summary and all Section reviews at