Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease, and its molecular pathogenesis remains poorly understood. Recently, emerging evidence demonstrates that the PI3K signaling transduction pathway is linked to the pathology of IPF. In this work, we rationally designed a new series of 4-methylquinazoline derivatives as highly potent PI3K inhibitors that significantly suppress the phosphorylation of the main PI3K downstream effectors and displays marked antiproliferative activity in mouse MLg2908 lung fibroblasts. In a bleomycin-induced mouse pulmonary fibrosis model, 5d from the series improved mouse lung function and slowed the progression of pulmonary fibrosis. Overall, this work promises a therapeutic potential for PI3K inhibitors to treat IPF.

中文翻译：

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发现基于4-甲基喹唑啉的PI3K抑制剂可用于特发性肺纤维化的潜在治疗。

特发性肺纤维化（IPF）是一种进行性且致命的肺部疾病，其分子发病机理仍然知之甚少。最近，新出现的证据表明PI3K信号转导途径与IPF的病理联系在一起。在这项工作中，我们合理地设计了一系列新的4-甲基喹唑啉衍生物作为强效PI3K抑制剂，可显着抑制主要PI3K下游效应子的磷酸化并在小鼠MLg2908肺成纤维细胞中显示出显着的抗增殖活性。在一博来霉素诱导的小鼠肺纤维化模型中，图5d从系列改善小鼠肺功能和减缓肺纤维化的进展。总的来说，这项工作有望为PI3K抑制剂治疗IPF带来治疗潜力。