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.
