211555-05-4

WHI-P97 inhibits the translocation of 5-lipoxygenase (5-LO) from the nucleoplasm to the nuclear membrane and consequently 5-LO-dependent leukotriene (LT) synthesis after IgE receptor/FcεRI crosslinking by >90 % at low micromolar concentrations. WHI-P97 (30 μM) stantially reduces the IgE/antigen-induced LTC4 release from mast cells.

WHI-P97 is very well tolerated in mice, with no signs of toxicity at dose levels ranging from 5 μg/kg to 50 mg/kg, and LD ₁₀ is not reached at a 50 mg/kg dose level when administered as a single ip or iv bolus dose. WHI-P97 (iv injection; 40 mg/kg; single dose) has an elimination half-life (t _1/2 ) of 58.9 min and systemic clearance (CL) of 891 ml/h/kg in CD-1 mice and at _1/2 of 84.2 min and CL of 1513 ml/h/kg in BALB/ c mice. The values for AUC and C _max are 107.3 μM and 296.7 μM, respectively, in CD-1 mice. And the IC ₅₀ values are 58.4 μM and 212.7 μM , respectively, in BALB/c mice. The large volume of distribution are 322 ml/kg in CD-1 mice and 415 ml/kg in BALB/c mice. WHI-P97 (intraperitoneal injection; 40 mg/kg; 24 days) prevents ovalbumin-sensitized mice the development of airway hyper-responsiveness to methacholine in a dose-dependent fashion in mice. WHI-P97 inhibits the eosinophil recruitment to the airwa y lumen after the ovalbumin challenge in a dose-dependent fashion.