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Research from the Russell group in Angewandte Chemie reveals the Arylhydrocarbon Receptor as the molecular target of the utrophin modulator ezutromid

A collaboration between the Russell group (Chemistry and Pharmacology) and the Davies group (Physiology, Anatomy and Genetics) has identified, via a chemical proteomics and phenotypic profiling strategy, the arylhydrocarbon receptor (AhR) as the molecular target of ezutromid, the utrophin modulator that recently completed a Phase 2 clinical trial in Duchenne muscular dystrophy patients.

Ezutromid (formerly SMT C1100) was identified through phenotypic screening approach, and developed as a first-in-class utrophin modulator for the treatment of the severe muscle wasting disease Duchenne muscular dystrophy (DMD). The clinical trial showed promising efficacy and evidence of target engagement after 24 weeks of treatment, but these effects were not seen after the full 48 weeks of the trial. Without knowledge of the mechanism of action of ezutromid, it was difficult to rationalise the lack of sustained clinical efficacy, and development of ezutromid was discontinued.
In this work, we demonstrate through a series of target identification and validation studies that ezutromid binds to AhR with high affinity, and antagonism of AhR by ezutromid leads to utrophin upregulation, thereby confirming AhR as a viable target for utrophin functional replacement therapies. This work paves the way for the first target-based disease modifying drug discovery program in DMD.


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Oxford Times/Mail profile: Angela Russell
Angie was profiled in the Oxford Times and Mail on 5th December. The article explained how she began her career in medicinal chemistry and the ground-breaking regenerative medicine approach that her research is taking. Read full article:

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Poster prize for Rachel
Well done to Rachel Sim for winning a prize for her poster at the MSD for the UK sponsored symposium on 24th October.
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Poster prize for Rachel
Well done to Rachel Sim for winning a prize for her poster at the MSD for the UK sponsored symposium on 24th October.
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Congratulations Isabel
Many congratulations to Isabel Wilkinson who successfully defended her thesis on 21st October.
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Congratulations Daniel
Many congratulations to Daniel Lucy for successfully defending his thesis on 21st October.
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Congratulations Chris!

Many congratulations to Chris Lindsay, funded by the British Heart Foundation (BHF) Centre of Research Excellence, for handing in his DPhil thesis on 1st October.


Congratulations Dan!

Many congratulations to Daniel Lucy, funded by the British Heart Foundation (BHF) Centre of Research Excellence, for handing in his DPhil thesis this week.


Poster prize for Laurence Silpa

Congratulations to Laurence Silpa (pictured third from the left) who won 2nd prize for her poster presentation at the Oxford Stem Cell Institute (OSCI) symposium 2019.


Congratulations Isabel!

Well done to Isabel Wilkinson for successfully handing in her DPhil thesis on 16th September.


Poster prize for Rachel Sim

Congratulations to Rachel Sim, an Agency of Science, Technology and Research (A*STAR)-funded DPhil student, who was awarded the penultimate year poster prize at the chemical biology conference ChemBiOx 2019, in Oxford. Rachel presented her work on developing affinity and fluorescent probes to elucidate the mechanism of small molecule modulators of neurogenesis.


Presentation: AJR at the Tetrahedron Symposium
AJR was invited to present at the Tetrahedron Symposium on 20th June in Bangkok, Thailand.


AJR group summer dinner

Photograph of the AJR group at St John's College on 17th June.

Many congratulations to our Part IIs, Libby Brown, Jacob Locke-Gotel, Sophie Trott and Hannah Lawrence, for handing in their Part II theses on Friday 14th June.


Prize for Daniel Lucy

Congratulations to Daniel Lucy (pictured third from the top left) who won a prize for his talk at the Astra Zeneca sponsored Final Year Symposium held at the Department of Chemistry on 22nd/23rd May 2019.


Running for success in the Oxford Town and Gown 10km race

Well done to (pictured from left to right) Jacob Locke-Gotel, Dan Lucy, David Zimmer, Sebastien Galan, Libby Brown, and Isabel Wilkinson (not in photo) for running the Oxford Town and Gown 10km race on Sunday 12th May. The team was running to raise awareness of the AJR group's research towards the development of small molecule utropin modulators for the treatment of Duchenne Muscular Dystrophy (DMD).


Bronze award for Isabel Wilkinson at the STEM for Britain reception 2019

Many congratulations to Isabel who was awarded the Bronze award (Chemistry section) for her poster at the STEM for Britain exhibition at the House of Commons on Wednesday 13th March. STEM for BRITAIN aims to raise the profile of Britain's early-stage researchers at Westminster by engaging Members of both Houses of Parliament with current science, engineering and mathematics research being undertaken in the UK. Isabel presented her research on identifying drug targets for Duchenne Muscular Dystrophy, a project in collaboration with Prof Dame Kay Davies (DPAG) and Dr Kilian Huber (Nuffield Department of Medicine). Read the full press release.


Presentation: Dr Carole Bataille at the Syngenta PDRA Symposium
Well done to Carole for presenting an excellent talk to the Department on Thursday 21st February at the Syngenta-sponsored PDRA symposium. Her talk focused on the collaborative work, with the Rabbitts Group (MRC Weatherall Institute of Molecular Medicine, WIMM) recently published in Nature Communications (see featured publication).

New AJR research group website launched
A new research group website was launched on Monday 25th February 2019.


Presentation: AJR invited to speak at the University of Leicester
AJR was invited to give a guest seminar entitled at the Department of Chemistry, University of Leicester on 30th January 2019.