Farnaby Research Group

Thanks Sai!

Discovery of a CNS active GSK3 degrader using orthogonally reactive linker screening Bifunctional targeted protein degraders, also known as Proteolysis Targeting Chimeras (PROTACs), are an emerging drug modality that may offer a new approach to understand and treat neurodegenerative d...

New preprint out co-led Nur Kocaturk along with colleagues at University of Dundee and Bio-Techne showing a direct-to-biology discovery of a brain penetrant degrader of GSK3. Congratulations to all!
chemrxiv.org/engage/chemr...

Special mentions to @nurkocaturk.bsky.social and @holmqvist89.bsky.social for driving this project, key collaborators Calum Sutherland and Kevin Read and their groups in Dundee and our awesome collaborators and supporters at @biotechne.bsky.social

A key learning: modest brain penetration combined with rapid on-target degradation kinetics was sufficient for activity in brain, highlighting opportunities for those who want to degrade proteins in the CNS and perhaps cautions for those who don’t. 6/7

Further profiling validated our best hits as cellular and in vivo quality degrader probes that we hope will help researchers further understand this target implicated in several neurodegenerative disease related pathways. 5/7

Once we had the assay, method and linker toolbox established we synthesised, screened and analysed data, from scratch, in 5 days, to identify potential hits. 4/7

We used a new approach we called ‘orthogonally reactive linker screening’, to vary all elements of a bifunctional via multi-step synthesis in a well: E3 binder, POI binder, linker and conjugation chemistry. We did this in context of discovering GSK3 degraders. 3/7

If you like TPD, direct-to-biology approaches, new chemical probe methods, induced proximity or Central Nervous System drug discovery then this is for you! 2/7

Discovery of a CNS active GSK3 degrader using orthogonally reactive linker screening Bifunctional targeted protein degraders, also known as Proteolysis Targeting Chimeras (PROTACs), are an emerging drug modality that may offer a new approach to understand and treat neurodegenerative d...

Excited to share the Farnaby Group’s first pre-print, detailing our approach to plate-based bifunctional chemical probe discovery, identifying a brain active PROTAC directly from a single screen. 1/7

chemrxiv.org/engage/chemr...

A chemical toolbox to investigate protein-protein interactions and their impact on mitophagy signalling - EASTBIO | University of Dundee, UK A PhD project at the University of Dundee

We have a new fully funded PhD position in the lab. Looking forward to finding excellent talents to work with! Check out the link for more info ⤵️.

www.dundee.ac.uk/phds/opportu...

Farnaby research group is on BlueSky now. Keep following our group updates!