Oclacitinib is an oral JAK inhibitor that is a drug approved by the U.S. Food and Drug Administration (FDA) for use in canine atopic dermatitis (AD). The U.S. FDA and the European Medical Association have approved a number of JAK inhibitors, including baricitinib, ruxolitinib, federatinib, tofacitinib, upadacitinib, oclacitinib, but some of these drugs are still being studied. Oclacitinib mainly shows activity against JAK1-dependent cytokines and also inhibits the function of JAK2-dependent cytokines. oclacitinib modifies the production of cytokines such as IL-4 and IL-13, which are crucial for B-cell proliferation and maturation in the pathogenesis of pemphigus foliaceus. Oclacitinib could interdict the effects of IL-6, a cytokine involved in the Toll-like receptor 4-originated signaling pathway in the bladder epithelial cells, and IL-8, which could theoretically contribute to a decreased defense against the urinary pathogens[1-4].
Oclacitinib is a novel Janus kinase (JAK) inhibitor with activity against cytokines involved in allergy.
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.
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].
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].
[1] Xin P, et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. International Immunopharmacology, 2020; 80: 549-56.
[2] Kalantari Y, et al. A literature review on Janus kinase (JAK) inhibitors for the treatment of immunobullous disorders. International Immunopharmacology, 2022; 110: 108923.[3] Erickson S, et al. New and emerging treatments for inflammatory itch. Annals of Allergy, Asthma Immunology, 2020; 126: 13-20.
[4] Xu P, et al. Janus kinases (JAKs): The efficient therapeutic targets for autoimmune diseases and myeloproliferative disorders. European Journal of Medicinal Chemistry, 2020; 129: 112155.
