A novel multikinase inhibitor SKLB-YTH-60 ameliorates inflammation and fibrosis in bleomycin-induced lung fibrosis mouse models.

ABSTRACT:

Objectives

Idiopathic pulmonary fibrosis (IPF) is marked by the excessive accumulation of extracellular matrix, which participates in a variety of chronic diseases or injuries and seriously threatens human health. Due to the side effects of clinical drugs, there is still a need to develop novel and less toxic drugs to treat pulmonary fibrosis.

Materials and methods

SKLB-YTH-60 was developed through computer-aided drug design, de novo synthesis and high-throughput screening. We employed the bleomycin (BLM)-induced lung fibrosis animal models and used TGF-β₁ to induce the epithelial-mesenchymal transition (EMT) of A549 cells in vitro. Meanwhile, the protein expression of collagen I and the α-smooth muscle actin (α-SMA), E-cadherin, p-FGFR1, p-PLCγ, p-Smad2/3 and p-E

SUBMITTER: Liu H 

PROVIDER: S-EPMC8249783 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature