Description:

IC50: 10 nM for JAK1

Janus kinase (JAK) enzymes are involved in cell signaling pathways activated by cytokines dysregulated in allergy. PF-03394197 (Oclacitinib) is a novel Janus kinase inhibitor.

In vitro: PF-03394197 inhibited JAK family members by 50% at concentrations ranging from 10 to 99 nM and did not inhibit a panel of 38 non-JAK kinases. PF-03394197 was most potent at inhibiting JAK1. PF-03394197 also inhibited the function of JAK1-dependent cytokines involved in allergy and inflammation as well as pruritus. PF-03394197 had minimal effects on cytokines which did not activate the JAK1 enzyme in cells [1].

In vivo: PF-03394197 administered orally at a dose of 0.4–0.6 mg/kg twice daily was safe and efficacious in controlling the pruritus associated with allergic dermatitis. PF-03394197 provided itch relief within 24 h that persisted through the treatment period, with over 70% of the treated dogs achieving a >50% reduction in pruritus by day 7 [2].

Clinical trial: PF-03394197 (Oclacitinib) (APOQUEL?) has recently been approved in the United States and European Union for the control or treatment of pruritus associated with allergic dermatitis and the control or treatment of AD in dogs [1].

Reference:
[1] Gonzales AJ, Bowman JW, Fici GJ, Zhang M, Mann DW, Mitton-Fry M.  Oclacitinib (APOQUEL(?)) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy. J Vet Pharmacol Ther. 2014 Aug;37(4):317-24.
[2] Cosgrove SB, Wren JA, Cleaver DM, Martin DD, Walsh KF, Harfst JA, Follis SL, King VL, Boucher JF, Stegemann MR.  Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis. Vet Dermatol. 2013 Oct;24(5):479-e114.