| References: |
GNE-3511 is a potent and selective zipper kinase (DLK, MAP3K12) inhibitors.In vitro: . The high dose of inhibitor GNE-3511 resulted in a completesuppression of c-Jun phosphorylation, while the low dose reduced the number of p-c-Jun positive cells to an intermediate level. protected primary neurons in an in vitro axon degeneration assay as well as reduced phosphorylation of the downstream transcription factor c-Jun.
In vivo: GNE-3511 exhibites moderate (mouse, rat, and cynomolgus) to high (dog) in vivo plasma clearances, moderate volumes of distribution, short half-lives, and brain penetration sufficient to enable examination in animal models of neurodegeneration. |
