PF670462

PF-670462 is a small-molecule inhibitor of casein kinase 1 delta and epsilon (CK1δ/ε) developed by Pfizer for research use. It is widely used as a pharmacological probe in mammalian circadian biology due to its ability to modulate the phosphorylation of core clock components.

The compound acts by inhibiting CK1δ and CK1ε kinases, reducing phosphorylation of PERIOD (PER) proteins. This alteration affects the stability and subcellular localization of PER proteins, thereby modifying the negative feedback loop that governs circadian rhythms. In cellular assays, PF-670462 lengthens the circadian period and can shift the phase of clock gene expression. In mice and other rodents, administration has been reported to lengthen the free-running circadian period of locomotor activity, illustrating CK1δ/ε's role in clock timing.

PF-670462 is described as potent and relatively selective for CK1δ/ε, with limited activity on CK1α and many other kinases at typical research concentrations. Researchers use it to dissect the contribution of CK1δ/ε to circadian control and to explore links between clock machinery and downstream processes such as metabolism and cell cycle.

As a research chemical, PF-670462 is not approved for clinical use. It is distributed to licensed researchers through chemical suppliers and laboratories for in vitro and in vivo studies under appropriate biosafety conditions.