PF-5006739 is a potent inhibitor of casein kinases 1 delta (CK1δ) and 1 epsilon (CK1ε), key regulators of the suprachiasmatic nucleus (SCN) central clock and also linked to the development of drug addiction through PERIOD proteins (PER1–3) and dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) modulation. PF-5006739 has low nM in vitro potency for CK1δ/ε (IC50 values of 3.9 nM for CK1δ and 17.0 nM for CK1ε) and high kinome selectivity. PF-5006739 induced profound phase delays in circadian periodicity in both nocturnal and diurnal animal models and attenuated opioid drug-seeking behavior in a rodent operant reinstatement model.
