Table 4.
Effects of CK1-specific inhibitors in selected animal models.
| Process | Inhibitor | Model | Effects | Reference |
|---|---|---|---|---|
| Circadian rhythm | PF-670462 | Rat | Inhibition of CK1δ/ε yields perturbation of oscillator function leading to phase delays in circadian rhythms | (359) |
| PF-670462 | Rat | Chronic treatment with the CK1δ/ε specific inhibitor PF-670462 yields cumulative phase delays in circadian rhythms | (374) | |
| PF-670462 | Monkey | Inhibition of CK1δ/ε produces phase shifts in circadian rhythms of Cynomolgus monkeys | (375) | |
| PF-670462; PF-4800567 | Mouse | Whereas PF-670462 causes a significant phase delay in animal models of circadian rhythm, CK1ε-specific PF-4800567 only shows a minimal effect on the circadian clock | (273) | |
| CK01 | Mouse | Chronic administration of CK01 leads to a reversal of the anxiety-related behavior, and partial reversal of the depression-related phenotypes of the Clock mutant mouse | (370) | |
| PF-670462; PF-4800567 | Mouse | Selective inhibition of CK1δ acts as a potent in vivo regulator of the circadian clock and may represent a mechanism for entrainment of disrupted or desynchronized circadian rhythms | (278) | |
| PF-670462; PF-4800567 | Zebrafish | The use of a pan-CK1δ/ε inhibitor and a CK1ε-selective inhibitor revealed that activity of CK1δ is crucial for the functioning of the circadian timing mechanism in zebrafish at multiple levels | (283) | |
| Drug use disorder | PF-670462 | Rat | Inhibition of CK1δ/ε in the nucleus accumbens with the selective inhibitor PF-670462 blocks amphetamine-induced locomotion by regulating of the AMPA receptor phosphorylation | (376) |
| Sensitivity to opioids | PF-4800567 | Mouse | Co-administration of the CK1ε specific inhibitor of PF-4800567 increased the locomotor stimulant response to methamphetamine and fentanyl | (377) |
| Alcoholism | PF-670462 | Rat | The inhibition of CK1δ/ε with systemic PF-670462 injections dose-dependently prevented the alcohol deprivation effect | (378) |
| Cancer | IC261 | Mouse | Inhibition of CK1 isoforms by IC261 influences the growth of induced pancreatic tumors in SCID mice | (339) |
| IC261 | Mouse | IC261 treatment blocks MYCN amplified neuroblastoma tumor growth in vivo | (346) | |
| D4476 | Mouse | Inhibition of CK1α activity leads to reduced Rps6 phosphorylation and activation of p53, resulting in selective elimination of leukemia cells | (348) | |
| Spinal inflammatory pain transmission | IC261; TG003 | Mouse | Both compounds decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in inflammatory pain models | (379) |