2. Academic Validation
  3. Z226407860 attenuates HDM-induced airway epithelial injury and ROS accumulation via RBX1 inhibition

Z226407860 attenuates HDM-induced airway epithelial injury and ROS accumulation via RBX1 inhibition

  • Bioorg Chem. 2026 Jun 5:173:109646. doi: 10.1016/j.bioorg.2026.109646.
Ling Feng 1,  Li Li 2,  Yale Sun 3,  Yuan Yin 3,  Yuan Zhong 4,  Yuan Ma 5
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital with Nanjing Medical University, China.; State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, Macau 999078, SAR, China.
  • 2 School of pharmacy, Jiangsu Health Vocational College, China.
  • 3 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital with Nanjing Medical University, China.
  • 4 School of pharmacy, Jiangsu Health Vocational College, China.. Electronic address: [email protected].
  • 5 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital with Nanjing Medical University, China.. Electronic address: [email protected].
PMID: 41707388 DOI: 10.1016/j.bioorg.2026.109646
Abstract

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.

Keywords

Airway epithelial injury; Asthma; RBX1; ROS; Targeted therapy; Virtual screening.

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