BACKGROUND AND PURPOSE Idiopathic pulmonary fibrosis (IPF) is characterized by excess accumulation of extracellular matrix, is involved in many chronic diseases or injuries and greatly threatens human health. However, clinical drugs have unexpected side effects. The development of novel, less toxic drugs to treat pulmonary fibrosis remains an urgent need. EXPERIMENTAL APPROACH YTH-60 was developed via computer-aided drug design, de novo synthesis and high-throughput screening. The biochemical, pharmacodynamic and toxicological profifiles of YTH-60 were investigated using kinase and cell viability assays, a bleomycin-induced mouse pulmonary fibrosis model and a TGF-β1 induced epithelial-mensenchymal transition in A549 cell . KEY RESULTS YTH-60 displayed marked antiproliferative activity in fibroblasts and A549 cells. YTH-60 suppressed the TGF-β1 induced protein expression of collagen type I and alpha smooth muscle actin (α-SMA) in vitro. Moreover, intraperitoneal administration of YTH-60 at a dose of 15 and 30 mg-1•kg-1•day•-1 for 2 weeks effectively alleviated the degree of fibrosis in a bleomycin-induced mouse pulmonary fibrosis model without obvious side effects. Importantly, YTH-60 demonstrated decent bioavailability (F=17.86%) and suitable eliminated half-life time (T1/2 =8.03h). CONCLUSION AND IMPLICATIONS YTH-60, a novel multikinase inhibitor, shows therapeutic potential for treating pulmonary fibrosis, and warrants further investigation as a potential drug candidate.