950912-80-8

The casein kinase 1 (CK1) family of kinases regulate diverse processes, particularly related to circadian rhythms and sensitivity to amphetamines. PF-670462 is a potent inhibitor of the CK1 isoforms CK1ε and CK1δ (IC₅₀ = 7.7 and 14 nM, respectively). It less effectively inhibits a wide variety of related or common kinases. Through its effects on CK1, PF-670462 disrupts circadian rhythms in cells and animals. It also blocks the locomotor response to amphetamines in mice.

PF 670462 is a potent and selective casein kinase 1ε (CK1ε) and CK1δ inhibitor. PF 670462 has been shown to inhibit PER protein nuclear translocation causing phase shifts in circadian rhythms. PF 670462 attenuates methamphetamine-stimulated locomotion in vivo.

ChEBI: A hydrochloride salt resulting from the formal reaction of 3-[(3-chlorophenoxy)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine with 2 mol eq. of hydrogen chloride. It is a selectiv inhibitor of the delta- and epsilon-isoforms of casein kinase 1 (CK1delta and CK1epsilon).

PF-670462 is also termed as 4-[1-cyclohexyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-2-pyrimidinamine dihydrochloride). It participates in ceramide transfer between Golgi and ER (endoplasmic reticulum) compartments. PF-670462 affects actin filament consolidation. It also hinders the stability at the front edge of cells treated with N-formyl Met-Leu-Phe.

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[1] LORI BADURA. An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms under free-running and entrained conditions.[J]. ACS Applied Electronic Materials, 2007: 730-738. DOI: 10.1124/jpet.107.122846
[2] SIMA SMADJA STORZ. Casein kinase 1δ activity: a key element in the zebrafish circadian timing system.[J]. PLoS ONE, 2013: e54189. DOI: 10.1371/journal.pone.0054189
[3] CAMRON D BRYANT. A role for casein kinase 1 epsilon in the locomotor stimulant response to methamphetamine.[J]. Psychopharmacology, 2009, 203 4: 703-711. DOI: 10.1007/s00213-008-1417-z