General description
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 (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; Ki = 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.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
DLK
Reversible: yes
Packaging
Packaged under inert gas
Warning
Toxicity: Standard Handling (A)
Reconstitution
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Patel, S., et al. 2014. J. Med. Chem. 57, in press.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Molecular Weight: 440.49. Empirical Formula: C23H26F2N6O. Assay: ≥. 98% (HPLC). Quality Level: 100. form: solid. manufacturer/tradename: Calbiochem®. . storage condition: OK to freeze, protect from light. color: yellow. solubility: DMSO: 20 . mg/mL. storage temp.: 2-8°C. Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.- UPC:
- 12352200
- Condition:
- New
- Weight:
- 1.00 Ounces
- HazmatClass:
- No
- WeightUOM:
- LB
- MPN:
- 5331680001