Potent inhibitor of casein kinase 1epsilon/delta (CK1epsilon, IC50 = 7.7 nM, CK1delta, 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 CK1delta inhibition and not CK1epsilon.3 It improved cognitive performance and reduced amyloid load in various mouse models of Alzheimers 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
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