Uses
PF-5006739 is a potent and selective inhibitor of CK1δ/ε with IC50s of 3.9 nM and 17.0 nM, respectively. PF-5006739 is a potential therapeutic agent for a range of psychiatric disorders with low nanomolar in vitro potency for CK1δ/ε and high kinome selectivity. PF-5006739 attenuats opioid agent-seeking behavior in a rodent operant reinstatement model in animals in a dose-dependent manner[1]. PF-5006739 improves glucose tolerance in both diet-induced obesity (DIO) and genetic (ob/ob) mice models of obesity[2].
Biochem/physiol Actions
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.
IC 50
CK1δ: 3.9 nM (IC
50)
References
[1] Wager TT, et al. Casein kinase 1δ/ε inhibitor PF-5006739 attenuates opioid drug-seeking behavior. ACS Chem Neurosci. 2014 Dec 17;5(12):1253-65. DOI:
10.1021/cn500201x[2] Cunningham PS, et al. Targeting of the circadian clock via CK1δ/ε to improve glucose homeostasis in obesity.Sci Rep. 2016 Jul 21;6:29983. DOI:
10.1038/srep29983
