Farnaby Research Group
@farnabygroup.bsky.social
Chemical innovation for CNS diseases
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
March 10, 2025 at 1:01 PM
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
March 10, 2025 at 12:55 PM
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
March 10, 2025 at 12:54 PM
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
March 10, 2025 at 12:54 PM
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
March 10, 2025 at 12:53 PM
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
March 10, 2025 at 12:53 PM
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