JTE-852, a novel spleen tyrosine kinase inhibitor, blocks antigen-induced allergic reactions in rats.

Abstract

Conventional clinical treatments for allergy management remain suboptimal; new, orally available medications that improve a wide range of allergic signs have been desired. We previously demonstrated that JTE-852, a novel spleen tyrosine kinase inhibitor, potently and simultaneously suppresses secretion of granule contents, arachidonate metabolites, and cytokines from mast cells stimulated by immunoglobulin E-crosslinking. In the present study, we investigated the effects of JTE-852 in four rat models (sneezing, rhinorrhea, airway constriction, and airway inflammation) as representatives of allergy models. Rats were sensitized and challenged with antigen. Allergic reactions developed after challenge were detected. JTE-852 and current anti-allergic drugs (ketotifen, pranlukast, and prednisolone) were administered orally before challenge. JTE-852 showed significant blocking effects on antigen-induced allergic reactions in all models, indicating that JTE-852 in oral dosage form would improve a wide range of allergic signs. The current anti-allergic drugs, on the other hand, failed to display significant suppression in several models. Because JTE-852 suppresses the secretion of all three groups of allergic mediators from mast cells, it would be capable of targeting signs that current drugs cannot sufficiently relieve. We anticipate JTE-852 to be a promising new anti-allergic drug that is potentially more effective than conventional drugs.