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• W4310253610 abstract "Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease of unknown aetiology with limited treatment options. Currently, only two drugs, nintedanib and pirfenidone, are approved for the clinical treatment of IPF, but their efficacies are not satisfactory. Previous studies have shown that STAT3 might be a promising therapeutic target for IPF. Here, we designed several series of compounds and finally synthesized a total of 48 novel compounds as potential STAT3 inhibitors. Notably, compound 10K was the most promising compound with excellent inhibitory activity against STAT3 phosphorylation. Subsequently, the anti-pulmonary fibrosis effect of 10K was further investigated by TGF-β1-stimulated in vitro cell assay and bleomycin (BLM)-induced pulmonary fibrosis animal models. Specifically, compound 10K inhibited the TGF-β1 induced fibrotic response and blocked the epithelial-mesenchymal transition (EMT) of A549 cells, and its inhibitory effect was significantly better than that of Stattic. In addition, after oral administration of 10K, the symptoms of IPF in the lung tissue in the prevention and treatment mouse models were significantly reversed, and the efficacy was comparable to that of nintedanib. Moreover, 10K improved BLM-induced imbalance of immune microenvironment in lung tissue. Taken together, these results suggest that 10K could be a potential STAT3 inhibitor for the treatment of IPF." @default.
• W4310253610 created "2022-11-30" @default.
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• W4310253610 date "2023-01-01" @default.
• W4310253610 modified "2023-09-27" @default.
• W4310253610 title "Discovery of the novel Benzo[b]thiophene 1,1-dioxide derivatives as a potent STAT3 inhibitor against idiopathic pulmonary fibrosis" @default.
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• W4310253610 doi "https://doi.org/10.1016/j.ejmech.2022.114953" @default.
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