WHI-P131 is a novel dimethoxyquinazoline compound that is a potent inhibitor of Janus kinase-3- (JAK3)–dependent mast cell responses. In the present study, the authors investigated the anti-anaphylactic activity and pharmacokinetics of WHI-P131 in mice. After intraperitoneal (i.p.) administration of two consecutive bolus doses of 25 mg/kg injected 30 min apart at dose level of 25 mg/kg, WHI-P131 was rapidly absorbed with an observed Cmaxof 82.6 &mgr;M, which is higher than the target concentration of 30 &mgr;M, at which WHI-P131 abrogates mast cell responses in vitro and the time to reach the maximum plasma concentration (tmax) was 10.0±2.9 min. At a nontoxic 50 mg/kg dose level, WHI-P131 prevented compound 48/80-induced mast cell histamine release and fatal anaphylaxis in mice. Further development of WHI-P131 may provide the basis for new and effective treatment as well as prevention programs for mast cell mediated allergic reactions in clinical settings.