Inhalable Carbonyl Sulfide Donor-Hybridized Selective Phosphodiesterase 10A Inhibitor for Treating Idiopathic Pulmonary Fibrosis by Inhibiting Tumor Growth Factor-β Signaling and Activating the cAMP/Protein Kinase A/cAMP Response Element-Binding Protein (CREB)/p53 Axis.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a debilitating, incurable, and life-threatening disease that lacks effective therapy. The overexpression of phosphodiesterase 10A (PDE10A) plays a vital role in pulmonary fibrosis (PF). However, the impact of selective PDE10A inhibitors on the tumor growth factor-β (TGF-β)/small mother against decapentaplegic (Smad) signaling pathway remains unclear. Herein, we have exploited a novel carbonyl sulfide (COS)/hydrogen sulfide (H₂S)-donor hybrid PDE10A inhibitor called COS-2080 with a well-defined mechanism of H₂S-releasing action. It exhibited highly potent inhibitory activity against PDE10A and excellent PDE subfamily selectivity. Moreover, COS-2080 demonstrated significant antifibrotic effects by inhibiting cell prol

SUBMITTER: Wang Q 

PROVIDER: S-EPMC11729434 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature