Small-molecule degraders for Nudix Hydrolase 5, NUDT5

Novel degrader molecules that degrade rather than inhibit human NUDT5 for therapeutic benefit.

Applications: Treatment of cancer, inflammatory and metabolic diseases

Features	Benefits
Exploits a novel scaffolding role of NUDT5 in purine metabolism, which is dependent on its scaffolding function rather than its catalytic activity	Broad targeting potential through its scaffolding interactions: targeting of PPAT exemplified, but potentially can be extended to other pathway members, such as GART, PAICS, ATIC, PFAS, HPRT1, SAICAR, AICAR
Heterocycle-containing linker connecting NUDT5 with CRBN E3 ligase complex	Provides balance of properties for efficient degradation and excellent solubility
PROTAC linker could connect NUDT5 to any degradation pathway, i.e., not only via E3 ligase	Customisable degradation based on specific needs
Can be administered in combination with another compound	Reducing side effects or toxicity of a second drug administered in treatment of cancer, inflammatory, autoimmune or metabolic disorder