PF-670462 dihydrochloride
Casein kinase 1δ/ε inhibitor / Potent inhibitor of casein kinase 1ε/δ (CK1ε, IC50 = 7.7 nM; CK1δ, IC50 = 14 nM).1 It is a circadian clock modifier that caused robust phase delays in rats1 and Cynomolgus monkeys2. PF-670462 caused nuclear retention of the clock protein PER resulting in period lengthening in a phase-specific manner that was dependent on CK1δ inhibition and not CK1ε.3 It improved cognitive performance and reduced amyloid load in various mouse models of Alzheimer’s disease.4-6 PF-670462 slowed the progression of and increased survival of chronic lymphocytic leukemia in mice alone and in combination with Ibrutinib.7
Biochemicals & reagents
950912-80-8
1) Badura et al. (2007), An Inhibitor of Casein Kinase I? Induces Phase Delays in Circadian Rhythms under Free-Running and Entrained Conditions; J. Pharmacol. Exp. Ther. 322 730 2) Sprouse et al. (2009), Inhibition of casein kinase I epsilon/delta produces phase shifts in the circadian rhythms of Cynomolgus monkeys; Psychopharmacology (Berl) 204 735 3) Meng et al. (2010), Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes; Proc. Natl. Acad. Sci. USA 107 15240 4) Adler et al. (2019), Therapeutic Targeting of Casein Kinase 1?/? in an Alzheimer's Disease Mouse Model; J. Proteome Res. 18 3383 5) Sundaram et al. (2019), Inhibition of casein kinase 1? improves cognitive-affective behavior and reduces amyloid load in the APP-PS1 mouse model of Alzheimer's Disease; Sci. Rep 9 13743 6) Mahoney et al. (2021), Inhibition of casein kinase 1?/? improves cognitive performance in adult C57BL/6J mice; Sci. Rep. 11 4746 7) Janovska et al. (2018), Casein kinase 1 is a therapeutic target on chronic lymphocytic leukemia; Blood 131 1206
-20°C
TARGET: Kinase -- RESEARCH AREA: Circadian clock; Neuroscience -- DISEASE AREA: Neurodegeneration; Cancer