IPF是一种渐进、致死性肺病，药物治疗是控制早、中期患者病情发展的主要手段。利用与IPF发病机制密切关联的靶标，寻找新型药物候选物具有重要意义。本课题前期研究中，通过分析TGF-β1及其I、II型受体细胞膜外结合域（TGFβR-ECD）的三维结构，建立这三个靶点的药效团模型，并从本实验室中药单体化合物数据库筛选到苯并呋喃类小分子化合物TT01。根据前期研究结果，我们提出假说：TT01很可能通过结合TGF-β及TGFβR-ECDs，抑制复合物形成中的配体-受体和/或受体-受体间相互作用（PPI），阻滞TGF-β信号转导，从而产生治疗IPF的药理学活性。本课题将从分子、细胞、整体实验动物水平，明确TT01对肺纤维化病理生理关键环节的作用方式及分子靶标，阐明其药理学作用机制，揭示其治疗IPF的潜在药用价值。

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease, and drug treatment is the main strategy to control the development of the disease in the early and middle stages. It is very important to find new drug candidates by exploiting targets that are closely related to the pathogenesis of IPF. In the preliminary study of this project, by analyzing the three-dimensional structure of TGF-β1 and its type I and II receptor extracellular domains (TGFβR-ECDs), the pharmacophore model of the three targets was established and used for inhibitor screening from an in-house Chinese herbal compound database. TT01, a benzofuran compound, was screened out from the compound database. Based on the results of previous pharmacodynamic and mechanistic experiments, we hypothesized that TT01 is likely to bind and block the protein-protein interactions (PPI) in the TGF-β-TGFβR-ECD complex to interrupt TGF-β signal transduction, resulting in pharmacological activity to treat IPF. This project will verify the mode of action and molecular targets of TT01 on the formation of TGF-β-TGFβRs complex, the key pathophysiology process of fibrosis, from series of experiments at the level of molecules, cells and experimental animals, and reveal its drugable value in the treatment of IPF in the future.