Wang Xin, Ren Rui, Xu Zehui, Huang Haidi, Jiang Wanglin, Ma Jinbo
School of Pharmacy, Binzhou Medical University, Yantai, China.
Medicine & Pharmacy Research Center, Binzhou Medical University, Yantai, China.
Front Pharmacol. 2021 Jul 19;12:693906. doi: 10.3389/fphar.2021.693906. eCollection 2021.
Tirbanibulin (KX-01) is the first clinical Src inhibitor of the novel peptidomimetic class that targets the peptide substrate site of Src providing more specificity toward the Src kinase. This study assessed the impact of KX-01 on cobalt chloride (CoCl)-treated L929 cells and bleomycin (BLM)-induced pulmonary fibrosis in rats to evaluate the efficacy of this compound and , respectively. In CoCl-treated L929 cells, KX-01 significantly reduced the expression of smooth muscle actin (α-SMA), collagen I, collagen III, hypoxia inducing factor (HIF-1α), signal transducers and transcriptional activators (p-STAT3), and p-Src. In BLM-induced pulmonary fibrosis rats, KX-01 reduced pathological scores, collagen deposition, α-SMA, collagen I, collagen III, p-Src, HIF-1α, and p-STAT3. Overall, these findings revealed that KX-01 can alleviate experimental pulmonary fibrosis via suppressing the p-SRC/p-STAT3 signaling pathways.
替尔泊替尼（KX-01）是新型拟肽类的首个临床Src抑制剂，它作用于Src的肽底物位点，对Src激酶具有更高的特异性。本研究分别评估了KX-01对氯化钴（CoCl）处理的L929细胞和博来霉素（BLM）诱导的大鼠肺纤维化的影响，以评价该化合物的疗效。在CoCl处理的L929细胞中，KX-01显著降低了平滑肌肌动蛋白（α-SMA）、胶原蛋白I、胶原蛋白III、缺氧诱导因子（HIF-1α）、信号转导子和转录激活子（p-STAT3）以及p-Src的表达。在BLM诱导的肺纤维化大鼠中，KX-01降低了病理评分、胶原蛋白沉积、α-SMA、胶原蛋白I、胶原蛋白III、p-Src、HIF-1α和p-STAT3。总体而言，这些发现表明KX-01可通过抑制p-SRC/p-STAT3信号通路减轻实验性肺纤维化。
