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Oclacitinib ( APOQUEL ® ) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy
Author(s) -
Gonzales A. J.,
Bowman J. W.,
Fici G. J.,
Zhang M.,
Mann D. W.,
MittonFry M.
Publication year - 2014
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12101
Subject(s) - janus kinase , janus kinase 2 , cytokine , proinflammatory cytokine , kinase , allergy , immunology , chemistry , janus kinase 1 , inflammation , pharmacology , medicine , biochemistry
Janus kinase (JAK) enzymes are involved in cell signaling pathways activated by various cytokines dysregulated in allergy. The objective of this study was to determine whether the novel JAK inhibitor oclacitinib could reduce the activity of cytokines implicated in canine allergic skin disease. Using isolated enzyme systems and in vitro human or canine cell models, potency and selectivity of oclacitinib was determined against JAK family members and cytokines that trigger JAK activation in cells. Oclacitinib inhibited JAK family members by 50% at concentrations (IC 50 's) ranging from 10 to 99 n m and did not inhibit a panel of 38 non‐JAK kinases (IC 50 's > 1000 n m ). Oclacitinib was most potent at inhibiting JAK1 (IC 50 = 10 n m ). Oclacitinib also inhibited the function of JAK1‐dependent cytokines involved in allergy and inflammation (IL‐2, IL‐4, IL‐6, and IL‐13) as well as pruritus (IL‐31) at IC 50 's ranging from 36 to 249 n m . Oclacitinib had minimal effects on cytokines that did not activate the JAK1 enzyme in cells (erythropoietin, granulocyte/macrophage colony‐stimulating factor, IL‐12, IL‐23; IC 50 's > 1000 n m ). These results demonstrate that oclacitinib is a targeted therapy that selectively inhibits JAK1‐dependent cytokines involved in allergy, inflammation, and pruritus and suggests these are the mechanisms by which oclacitinib effectively controls clinical signs associated with allergic skin disease in dogs.