CQMUH-011 mitigated LPS-induced acute lung injury in neonatal rabbits.

Neonatal sepsis-associated acute lung injury (ALI) remains a major clinical challenge. This study investigated the protective effects of a novel small-molecule compound, CQMUH-011, in a neonatal rabbit model of hyper-acute endotoxin shock with secondary ALI. Neonatal rabbits were intraperitoneally injected with lipopolysaccharide (50 mg/kg), followed by CQMUH-011 (75, 225, 675 µg/kg) or dexamethasone (Dex, 1.5 mg/kg) at 0.5 h. Over a 10-hour observation period, despite a non-significant trend in overall survival, CQMUH-011 dose-dependently mitigated neurological deficits, restored blood gas balance, enriched the phospholipid pool, reduced inflammatory lung injury and improved alveolar expansion. At the mRNA level, CQMUH-011 suppressed proinflammatory cytokines and upregulated surfactant-associated enzymes. The lung-protective effects of CQMUH-011 were comparable to those of Dex, or better on selected endpoints. Exploratory transcriptomic profiling suggested CQMUH-011 may function by downregulating multiple inflammatory pathways concurrent with the potential modulation of phosphatidylinositol 3-kinase/protein kinase B-dependent cytoprotection, cytoskeletal remodeling, and intercellular junction reinforcement. However, these transcriptomic signatures currently lack confirmatory protein-level testing. In conclusion, CQMUH-011 demonstrates preliminary lung-protective effects in this acute neonatal endotoxin shock paradigm. Rather than a definitive therapeutic candidate, CQMUH-011 represents an early-stage proof-of-concept molecule requiring extensive future pharmacokinetic characterization and mechanistic validation to establish its translational potential.