vx-770 and Pulmonary-Fibrosis

Thirty-one 4-oxoquinoline-3-carboxamides derivatives were synthesized and evaluated for their anti-fibrotic activities by the inhibition of TGF-β1-induced total collagen accumulation and anti-inflammatory activities by the inhibition of LPS-stimulated TNF-α production. Among them, three compounds (10a, 10l and 11g) exhibited potent inhibitory effects on both TGF-β1-induced total collagen accumulation and LPS-stimulated TNF-α production. Furthermore, oral administrations of 10l at a dose of 20 mg/kg/day for 4 weeks effectively alleviated lung inflammation and injury, and decreased lung collagen accumulation in bleomycin-induced pulmonary fibrosis model. Histopathological evaluation of lung tissue confirmed 10l as a potential, orally active agent for the treatment of pulmonary fibrosis.

Topics: 4-Quinolones; Animals; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Bleomycin; Cells, Cultured; Collagen; Lipopolysaccharides; Pneumonia; Pulmonary Fibrosis; Rats; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha