AZD0449

AZD0449 is a potent and highly selective Janus kinase 1 (JAK1) inhibitor developed by Rigel Pharmaceuticals and later developed by AstraZeneca for the treatment of asthma. It demonstrates an IC50 of 2.4 nM for JAK1 with >50-fold selectivity over TYK2 and JAK2, and no inhibition against JAK3[1]. The compound inhibits multiple JAK1-dependent cytokine signaling pathways critical for asthma pathogenesis, including IL-4, IL-5, IL-13, and thymic stromal lymphopoietin (TSLP) pathways[2]. AZD0449 is designed for **inhalation delivery** and exhibits favorable pharmacokinetic properties including low systemic exposure, medium-to-long terminal lung half-life (34 hours), and significant lung retention after intratracheal administration[2][3]. In preclinical studies, the compound demonstrated efficacy in reducing eosinophilia in the lung and the late asthmatic response in ovalbumin-challenged rat models[1][2].