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PF-670462 is a potent and selective inhibitor of CK1ε and CK1δ with IC50 value of 80 nM and 13 nM, respectively [1].

CK1ε and CK1δ 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 CK1ε  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 μM, the period in WT fibroblast cells extended to 33 h [3].

In WT, Ck1ε?/? and Ck1εtau mice, PF-670462 (10 mg/kg/d) significantly lengthened the period of activity rhythms in all three genotypes (WT: 0.44 h, Ck1εtau: 0.39 h, Ck1ε?/?: 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 Ck1ε?/? mice, which suggested that the effect of CK1δ on the circadian period [3].

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