A cell-permeable, orally bioavailable, blood-brain barrier permeant 2,6-diaminopyridine based compound that acts as a highly potent and selective inhibitor of dual leucine zipper kinase inhibitor (DLK; Ki = 500 pM). Exhibits an ideal balance of metabolic stability, potency, and efflux properties. Displays high selectivity over JNK (IC = 129, 514, and 364 nM for JNK1, 2, and 3, respectively) and MLK (IC = 67.8, 767, and 602 nM for MLK1, 2, and 3, respectively). Does not affect the activities of MKK4 and MKK7 (IC >5 microM). Protects neurons in an in vitro axon degeneration assay (IC = 107 nM). Also shown to reduce levels of phosphorylated c-Jun in retina and offer protection in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MTPT) model of Parkinson′s disease. Exhibits desirable pharmacokinetic properties (t1/2 = 0.6 h; CLp = 56 ml/min/kg in mice; 1 mg/kg, i.v., or 5 mg/kg; p.o.).Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.
Synonyms: DLK Inhibitor, GNE-3511 - Calbiochem; MAP3K12 Inhibitor, GNE-3511, Dual Leucine Zipper Kinase, GNE-3511, GNE3511, GNE 3511, 2-((6-(3,3-Difluoropyrrolidin-1-yl)-4-(1-(oxetan-3-yl)piperidin-4-yl)pyridin-2-yl)amino)isonicotinonitrile
Molecular Formula: C23H26F2N6O
Molecular Weight: 440.49
Linear Structural Formula: C23H26F2N6O
Purity: >=98% (HPLC)
Biochem Physiol Actions: Reversible: yes
Legal Information: CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Other Notes: Patel, S., et al. 2014. J. Med. Chem. 57, in press.