SB 431542,301836-41-9,IC-0237191

SB-431542, a small molecule inhibitor of the type I TGF-β receptor, blocks intracellular mediators of TGF-1 signaling, which leads to decreased TGF-β1–mediated proliferation, cytokines and collagen expression. In clinical settings, SB-431542 is widely used to treat respiratory asthma, and inhibits proliferation and synthesis of adventitial fibro in the process of pulmonary vascular remodeling.[1]
In vitro study indicated that SB-431542 is able to inhibit ALK5 with an IC50 of 94 nM and other type I receptors, such as ALK4. Although SB-431542 inhibited ALK4 with an IC50 of 140 nM. Moreover, SB-431542 inhibited TGF-β1–induced collagen Iα1 and PAI-1 mRNA with IC50 values of 60 and 50 nM, respectively. In addition, SB-431542 inhibited TGF-β1–induced fibronectin mRNA and protein with IC50 values of 62 and 22 nM, respectively. These data demonstrate for the first time that ALK5 activity is required for TGF-β1 regulation of extracellular matrix markers FN, collagen Iα1, and PAI-1 mRNA.[1]
In vivo study demonstrated that SB-431542 has the capacity to inhibit TGF-β1-induced gene expression. SB-431542 is recognized as a important inhibitor of the TGF-β1 receptors in blocking TGF-β1/Smads signal pathways in vascular remodeling. Moreover, hypoxia-induced vascular remodeling can significantly increase the amount of cytokines and collagen in vascular adventitia. However, after the treatment of SB-431542, attenuation of the fibrosis promoting effects of TGF-β1, including TGF-β1-induced cell proliferation, cell motility, cell migration and cell synthesis were observed. Therefore, it is significant to the identify the potential of SB-431542 for the treatment of hypoxia-induced pulmonary hypertension.[2]