Abstract
Because TGF-β is central to the progression of fibrosis, selective inhibition of this signaling pathway could provide a novel treatment for many fibrotic diseases. Small molecule inhibitors of the kinase activity of the TGF-β type I receptor (ALK5) have been developed by several companies and institutions. These inhibitors prevent the phosphorylation of the Smad proteins and many if not most of the sequelae following TGF-β release and activation. Thus, it has been demonstrated that these inhibitors prevent the extra-cellular matrix accumulation and organ destruction associated with fibrosis. The effectiveness of these inhibitors in several animal models suggests broad application in many fibrotic diseases. However, due to the pleiotropic activity of TGF-β there may be unwanted side effects of TGF-β type I receptor kinase inhibition, especially when considering chronic therapy
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Laping, N.J., Huet, S. (2006). TGF-β Receptor Kinase Inhibitors for Treatment of Fibrosis. In: Dijke, P.t., Heldin, CH. (eds) Smad Signal Transduction. Proteins and Cell Regulation, vol 5. Springer, Dordrecht. https://doi.org/10.1007/1-4020-4709-6_22
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