PF-670462

Short Summary : CK1 ?/? inhibitor

Category : Stem Cell|CK1

Purity : 0.9958

CAS Number : 950912-80-8

Formula : C19H22Cl2FN5

Molecular Weight : 410.32

SMILE : C1CCC(CC1)N2C=NC(=C2C3=NC(=NC=C3)N)C4=CC=C(C=C4)F.Cl.Cl

Solubility : >20.5mg/mL in DMSO

Storage : Store at -20°C

Description : PF-670462 is a potent and selective inhibitor of CK1? and CK1? with IC50 value of 80 nM and 13 nM, respectively [1].CK1? and CK1? belong to the casein kinase 1 family which is serine/threonine-selective enzyme and plays an important role in regulating circadian rhythm [1].In COS-7 cells cotransfected with GFP-tagged PER3 and the human CK1? enzyme, PF-670462 inhibited PER3 nuclear translocation in a concentration-dependent way [2]. In primary lung fibroblast cells obtained from WT mice, PF-670462 significantly lengthened the circadian period in a dose-dependent way. And with a dose of 1 ?M, the period in WT fibroblast cells extended to 33 h [3].In WT, Ck1?-/- and Ck1?tau mice, PF-670462 (10 mg/kg/d) significantly lengthened the period of activity rhythms in all three genotypes (WT: 0.44 h, Ck1?tau: 0.39 h, Ck1?-/-: 0.42 h). In WT mice, the activity onset occurred 10.4 h after 24 d of treatment. Also, PF-670462 caused identical period lengthening in WT and Ck1?-/- mice, which suggested that the effect of CK1? on the circadian period [3]. References:[1]. Walton KM, Fisher K, Rubitski D, et al. Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J Pharmacol Exp Ther, 2009, 330(2): 430-439. [2]. Badura L, Swanson T, Adamowicz W, et al. An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms under free-running and entrained conditions. J Pharmacol Exp Ther, 2007, 322(2): 730-738.[3]. Meng QJ, Maywood ES, Bechtold DA, et al. Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. Proc Natl Acad Sci U S A, 2010, 107(34): 15240-15245.

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