Targeting JAK-3 with WHI-P97 for Treatment of Asthma

DESCRIPTION (provided by applicant): The rationally designed Janus kinase 3 (JAK3) inhibitor 4-(3',5'-dibromo-4'-hydroxyphenyl)- anmino-6,7-dirnethoxyquinazoline (WHI-P97) exhibits potent in vivo biologic activity in a mouse model of allergic asthma at nontoxic dose levels. Further development of WHI-P97 may therefore provide the basis for new and effective treatment as well as prevention programs for allergic asthma. Our proposed research is aimed at developing clinically applicable formulations of WHI-P97. Under SPECIFIC Aim 1, we will develop oral suspension formulations of WHI-P97 for systemic administration. The primary goal of the proposed research is to establish effective methods aimed at improving its oral bioavaitabitity and develop a clinically applicable oral dosage formulation of HI-443. Under SPECIFIC AIM 2, we will develop inhaler formulations of WHI-P97 for direct administration through the airway. Commercially available aerosol, dry powder inhalers and nebulizers will be evaluated for direct delivery of WHI-P97 to the airways and lungs. Under SPECIFIC AIM 3, we will study the safety and efficacy of lead WHI-P97 formulations in a mouse model of allergic asthma. The successful completion of the proposed research will provide the foundation for further translational research that may lead to new and effective methods for treatment of allergic asthma.