Sigma-Aldrich Dlk Inhibitor, Gne-3511

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

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; 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 anin vitroaxon 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 anin vitroaxon 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: yesPrimary Target
DLKReversible: 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.CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany