Z226407860

Asthma is characterized by airway inflammation and epithelial barrier dysfunction, yet the underlying molecular mechanisms remain incompletely understood. Here, we identify RING-box protein 1 (RBX1) as a critical regulator of airway epithelial injury, whose expression is markedly elevated in asthma. Mechanistically, RBX1 expression correlates with increased reactive oxygen species (ROS) levels and epithelial barrier disruption, potentially involving its downstream target NOD-like receptor family pyrin domain containing 1 (NLRP1). Furthermore, we demonstrate that Z226407860, a novel small molecule, effectively suppresses RBX1 expression, mitigates ROS accumulation, and restores epithelial barrier integrity in house dust mite (HDM)-stimulated bronchial epithelial cells, without inducing cytotoxicity. Collectively, these findings reveal that RBX1 drives oxidative stress and epithelial injury in asthma and demonstrate that pharmacological inhibition of RBX1 with Z226407860 offers a potential therapeutic strategy to restore airway epithelial homeostasis.