5.33168

DLK Inhibitor, GNE-3511

• Sinónimos: DLK Inhibitor, GNE-3511, 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
• Fórmula empírica (notación de Hill): C₂₃H₂₆F₂N₆O
• Número de CAS: 1496581-76-0
• Peso molecular: 440.49
• Código UNSPSC: 12352200
• NACRES: NA.77

Propiedades

• Análisis: ≥98% (HPLC)
• Nivel de calidad: 100
• formulario: solid
• fabricante / nombre comercial: Calbiochem^®
• condiciones de almacenamiento: OK to freeze; protect from light
• color: yellow
• solubilidad: DMSO: 20 mg/mL
• temp. de almacenamiento: 2-8°C

Descripción

Descripción general

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; K_i = 500 pM). Exhibits an ideal balance of metabolic stability, potency, and efflux properties. Displays high selectivity over JNK (IC₅₀ = 129, 514, and 364 nM for JNK1, 2, and 3, respectively) and MLK (IC₅₀ = 67.8, 767, and 602 nM for MLK1, 2, and 3, respectively). Does not affect the activities of MKK4 and MKK7 (IC₅₀ >5 µM). Protects neurons in an in vitro axon degeneration assay (IC₅₀ = 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.).

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; K_i = 500 pM). Exhibits an ideal balance of metabolic stability, potency, and efflux properties. Displays high selectivity over JNK (IC₅₀ = 129, 514, and 364 nM for JNK1, 2, and 3, respectively) and MLK (IC₅₀ = 67.8, 767, and 602 nM for MLK1, 2, and 3, respectively). Does not affect the activities of MKK4 and MKK7 (IC₅₀ >5 µM). Protects neurons in an in vitro axon degeneration assay (IC₅₀ = 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.

Acciones bioquímicas o fisiológicas

Cell permeable: yes

Primary Target
DLK

Reversible: yes

Envase

Packaged under inert gas

Advertencia

Toxicity: Standard Handling (A)

Reconstitución

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Otras notas

Patel, S., et al. 2014. J. Med. Chem. 57, in press.

Información legal

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Información de seguridad

• Código de clase de almacenamiento: 11 - Combustible Solids
• Clase de riesgo para el agua (WGK): WGK 3
• Punto de inflamabilidad (°F): Not applicable
• Punto de inflamabilidad (°C): Not applicable