Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease with a median survival time of 3–5 years. Inaccurate diagnosis, limited clinical therapy and high mortality together indicate that the development of effective therapeutics for IPF is an urgent need. In recent years, it was reported that DDRs are potential targets in anti-fibrosis treatment. Based on previous work we carried out further structure modifications and led to a more selective inhibitor 47 by averting some fibrosis-unrelated kinases, such as RET, AXL and ALK. Extensive profiling of compound 47 has demonstrated that it has potent DDR1/2 inhibitory activities, low toxicity, good pharmacokinetic properties and reliable in vivo anti-fibrosis efficacy. Therefore, we confirmed that discoidin domain receptors are promising drug targets for IPF, and compound 47 would be a promising candidate for further drug development.

特发性肺纤维化 (IPF) 是一种慢性致命性肺部疾病，中位生存时间为 3-5 年。不准确的诊断、有限的临床治疗和高死亡率共同表明，迫切需要开发有效的 IPF 治疗方法。近年来，据报道，DDRs是抗纤维化治疗的潜在靶点。基于以前的工作，我们进行了进一步的结构修改，并通过避免一些与纤维化无关的激酶（如 RET、AXL 和 ALK）产生了更具选择性的抑制剂47 。对化合物47的广泛分析表明，它具有有效的 DDR1/2 抑制活性、低毒性、良好的药代动力学特性和可靠的体内抗纤维化功效。因此，我们证实盘状结构域受体是 IPF 的有希望的药物靶点，化合物47将是进一步药物开发的有希望的候选者。