General description
A cell-permeable, blood-brain-barrier-permeant, and orally available anilinopyrimidine compound that acts as a highly selective, potent, reversible, and ATP-competitive JNK inhibitor (IC50 = 67, 283, and 159 nM against JNK1, JNK2, and JNK3, respectively), exhibiting little or no activity toward a panel of more than 300 kinases, including p38 (IC50 >20 µM). Shown to inhibit c-jun phosphorylation both in STZ- (Streptozotocin, Cat. No. 572201) stimulated INS-1 β-pancreatic cells in vitro (IC50 = 216 nM) and in SNpc (substantia nigra pars compacta) TH- (tyrosine hydroxylase) positive neurons (by 75%; single p.o. dose of 30 mg/kg) from MPTP- (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treated mice in vivo. Effectively protects against SNpc TH-positive dopaminergic neuron loss in mice (46% vs. 27% loss with vehicle or 30 mg/kg SR-3306; p.o. b.i.d.) and rats (6-fold increase of vehicle control cell count; 10 mg/kg/day; s.c.) due to MPTP and 6-OHDA- (6-hydroxydopamine) intoxication, respectively, in vivo.
A cell-permeable, blood-brain-barrier-permeant, and orally available anilinopyrimidine compound that acts as a highly selective, potent, reversible, and ATP-competitive JNK inhibitor (IC50 = 67, 283, and 159 nM against JNK1, JNK2, and JNK3, respectively), exhibiting little or no activity toward a panel of more than 300 kinases, including p38 (IC50 >20 µM). Shown to inhibit c-jun phosphorylation both in STZ- (Streptozotocin, Cat. No. 572201) stimulated INS-1 β-pancreatic cells in vitro (IC50 = 216 nM) and in SNpc (substantia nigra pars compacta) TH- (tyrosine hydroxylase) positive neurons (by 75%; single p.o. dose of 30 mg/kg) from MPTP- (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treated mice in vivo. Effectively protects against SNpc TH-positive dopaminergic neuron loss in mice (46% vs. 27% loss with vehicle or 30 mg/kg SR-3306; p.o. b.i.d.) and rats (6-fold increase of vehicle control cell count; 10 mg/kg/day; s.c.) due to MPTP and 6-OHDA- (6-hydroxydopamine) intoxication, respectively, in vivo.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Other Notes
Chambers, J.W., et al. 2011. ACS Chem Neurosci.2, 198.Crocker, C.E., et al. 2011. ACS Chem. Neurosci.2, 207.
Packaging
Packaged under inert gas
10 mg in Glass bottle
Reconstitution
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Warning
Toxicity: Standard Handling (A)
This product has met the following criteria to qualify for the following awards: