Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family that regulates signal transduction downstream of receptors for the IL-23/IL-12 pathways and type I interferon family, where it pairs with JAK2 or JAK1, respectively[1]. PF-06826647 is a selective TYK2 inhibitor. It has been tested in moderate-to-severe psoriasis in a Phase II clinical trial. PF-06826647 was absorbed rapidly, with a median Tmax of 2 hours in the fasted state. The mean terminal half-lives (t1/2) for the 3 and 10 mg groups were 3.6 and 6.0 hours, respectively. For doses of 30 mg and above, the mean t1/2 ranged from 16.3 to 38.8 hours. The AUC from time zero extrapolated to infinite time (AUCinf) and Cmax increased in a greater than dose-proportional manner at PF-06826647 doses of 3-10 mg, and in a dose-proportional manner at doses of 400-1,600 mg. However, increases in AUCinf and Cmax were less than dose-proportional at doses of 10-400 mg. Variability in exposure based on the geometric coefficient of variation ranged from 25% to 67% for AUCinf and from 25% to 62% for Cmax[2].
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