PF-670462

• CAT Number: I005648
• CAS Number: 950912-80-8
• Molecular Formula: C19H20FN5 • 2HCl
• Molecular Weight: 410.3
• Purity: ≥95%
• Target: CK1
• Solubility: DMSO: ≥ 32 mg/mL
• Storage: Store at -20°C
• IC50: 7.7 nM
• IUPAC Name: 4-[3-cyclohexyl-5-(4-fluorophenyl)imidazol-4-yl]pyrimidin-2-amine;dihydrochloride
• InChI: InChI=1S/C19H20FN5.2ClH/c20-14-8-6-13(7-9-14)17-18(16-10-11-22-19(21)24-16)25(12-23-17)15-4-2-1-3-5-15;;/h6-12,15H,1-5H2,(H2,21,22,24);2*1H
• InChIKey: PSNKGVAXBSAHCH-UHFFFAOYSA-N
• SMILES: C1CCC(CC1)N2C=NC(=C2C3=NC(=NC=C3)N)C4=CC=C(C=C4)F.Cl.Cl

PF-670462 (Cat.No:I005648) is a potent (IC50 = 7.7 ± 2.2 nM) and selective (>30-fold with respect to 42 additional kinases) inhibitor of CK1ε in isolated enzyme preparations.  PF-670462, a selective CK1 ε/δ inhibitor, causes a significant phase delay in animal models of circadian rhythm; it remains unclear whether one of the kinases has a predominant role in regulating the circadian clock. In transfected whole cell assays, it caused a concentration-related redistribution of nuclear versus cytosolic PER. When tested in free-running animals, 50 mg/kg s.c. PF-670462 produced robust phase delays when dosed at circadian time (CT)9 (-1.97 ± 0.17 h). PF-670462 attenuates methamphetamine-stimulated locomotion in vivo.

Reference

[1]. Daniel I. Perez, Carmen Gil, Ana Martinez. Protein kinases CK1 and CK2 as new targets for neurodegenerative diseases. Med Res Rev.2011,31(6): 924-954. 

[2]. Jeffrey Sprouse, Linda Reynolds, Robin Kleiman, et al. Chronic treatment with a selective inhibitor of casein kinase I δ/ε yields cumulative phase delays in circadian rhythms . Psychopharmacology. 2010, 210( 4):569-576.

[3]. Qing-Jun Menga, Elizabeth S. Maywoodb, David A. Bechtolda, et al. Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. PNAS, 2010 ,107 (34) 15240-15245. 

[4]. Kevin M. Walton, Katherine Fisher, David Rubitski,et al. Selective Inhibition of Casein Kinase 1 Minimally Alters Circadian Clock Period. JPET, 2009, 30(2): 430-439.

[5]. Jeffrey Sprouse, Linda Reynolds, Terri A. Swanson, et al. Inhibition of casein kinase I ε/δ produces phase shifts in the circadian rhythms of Cynomolgus monkeys .Psychopharmacology. 2009, 204( 4): 735-742.