Small-Molecule Inhibitors Of Transforming Growth Factor-Beta Type I Receptor Kinase (Alk5)
Progress in Respiratory Research(2010)
Abstract
Transforming growth factor beta s (TGF-beta 1, TGF-beta 2 and TGF-beta 3) are members of a large superfamily of growth factors required for normal biological functions. As a consequence of this pleitrophy, dysregulation of this signaling pathway can play a major role in the pathogenesis of many diseases. Given this multiplicity of effects, inhibiting TGF-beta signaling has become an attractive strategy for drug discovery. There are several modes of inhibiting TGF-beta signaling: reducing the production of TGF-beta using antisense technology (1), inhibiting the extracellular activation of latent TGF-beta by blocking integrin-mediated activation (see chapter 33), and sequestering circulating TGF-beta using soluble TGF-beta receptor or monoclonal antibodies. In addition, a major effort has been invested in inhibiting receptor-mediated signaling using small-molecule inhibitors of the TGF-beta type I receptor (TGF-beta RI) kinase, and is the focus of this chapter.
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Key words
transforming growth factor
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