gne-3511

Description: GNE-3511 is a novel, highly potent and selective zipper kinase (e.g. DLK, MAP3K12) inhibitor with IC50 of 0.107 uM for DLK. Dual leucine zipper kinase (DLK, MAP3K12) was recently identified as an essential regulator of neuronal degeneration in multiple contexts. At high dose, 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. GNE-3511 protected primary neurons in an in vitro axon degeneration assay as well as reduced phosphorylation of the downstream transcription factor c-Jun. 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.

References: J Med Chem. 2015 Jan 8; 58(1):401-18.

GNE 3511; GNE3511; GNE-3511;

Chemical Name: 2-((6-(3, 3-difluoropyrrolidin-1-yl)-4-(1-(oxetan-3-yl)piperidin-4-yl)pyridin-2-yl)amino)isonicotinonitrile

SMILES Code: N#CC1=CC(NC2=NC(N3CC(F)(F)CC3)=CC(C4CCN(C5COC5)CC4)=C2)=NC=C1