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DN-1289

Chemical Structure : DN-1289

CAS No.: 3026597-15-6

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) Select Batch:

    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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