NU 9

NU 9 is a neuroprotective compound.¹ It is protective against toxicity induced by superoxide dismutase 1 (SOD1) containing the G93A mutation (SOD1^G93A) in PC12 cells (EC₅₀ = 0.3 µM). NU 9 (20 mg/kg per day) reduces SOD1^G93A levels in upper motor neurons in a model of amyotrophic lateral sclerosis (ALS) using mice expressing human SOD1^G93A.² It improves motor behavior in the hanging wire test, but not the rotarod, in the same model when administered at a dose of 100 mg/kg. NU 9 (10 and 20 mg/kg) increases survival in another human SOD1^G93A-expressing mouse model of ALS.¹ NU 9 also reduces the accumulation of amyloid-β (1-42) (Aβ42) oligomers in primary hippocampal neurons in a cathepsin B- and lysosomal-dependent manner.³

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1. Zhang, Y., Benmohamed, R., Zhang, W., et al. Chiral cyclohexane 1,3-diones as inhibitors of mutant SOD1-dependent protein aggregation for the treatment of ALS. ACS Med. Chem. Lett. 3(7), 584-587 (2012).

2. Genç, B., Gautam, M., Gözütok, Ö., et al. Improving mitochondria and ER stability helps eliminate upper motor neuron degeneration that occurs due to mSOD1 toxicity and TDP-43 pathology. Clin. Transl. Med. 11(2), e336 (2021).

3. Johnson, E.A., Nowar, R., Viola, K.L., et al. Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases. Proc. Natl. Acad. Sci. USA 122(10), e2402117122 (2025).