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DN-1289

Chemical Structure : DN-1289

CAS No.:

DN-1289 (DN1289)

Catalog No.: PC-49564Not For Human Use, Lab Use Only.

DN-1289 (DN1289) is a potent, selective and CNS-penetrant dual inhibitor of leucine zipper kinase (DLK, MAP3K12) and leucine zipper-bearing kinase (LZK, MAP3K13) with IC50 of 17 nM and 40 nM, respectively.

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Purity & Documentation Purity: >98% (HPLC)

Biological Activity

DN-1289 (DN1289) is a potent, selective and CNS-penetrant dual inhibitor of leucine zipper kinase (DLK, MAP3K12) and leucine zipper-bearing kinase (LZK, MAP3K13) with IC50 of 17 nM and 40 nM, respectively.
DN-1289 exhibits EC50 of 88 nM and 711 nM in DLK and LZK phospho c-Jun cellular assays, repectively.
DN-1289 dose-dependently protected axons and prevented caspase activation with full axon protection at 1 μM and partial effect at 0.1 and 0.3 μM in DRG neurons.
DN-1289 150 mg/kg (p.o., b.i.d.) significantly attenuated ONC-induced p-c-Jun elevation in the retina in mice.
DN-1289 (100 mg/kg, 5 days) exhibited neuroprotective effect in the SOD1G93A mouse model, with significant elevation of the p-c-Jun level and increased expression of genes associated with DLK pathway activation in the SOD1G93A spinal cords.

Physicochemical Properties

M.Wt 441.391
Formula C18H19F4N7O2
Appearance Solid
CAS No.
Storage
Solide Powder
-20°C 12 Months; 4°C 6 Months
In Solvent
-80°C 6 Months; -20°C 6 Months
Shipping
Solubility

10 mM in DMSO

Chemical Name/SMILES

5-(2-((1S,4S)-2-oxa-5-Azabicyclo[2.2.1]heptan-5-yl)-6-(3,3-difluoropyrrolidin-1-yl)pyrimidin-4-yl)-3-(difluoromethoxy)pyrazin-2-amine

References

1. Craig RA 2nd, et al. J Med Chem. 2022 Dec 5. doi: 10.1021/acs.jmedchem.2c01056.

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