Description
GW 788388 is a selective inhibitor of transforming growth factor-β (TGF-β) type 1 receptor (TGFBR1 or ALK5; IC
50 = 18 nM). It inhibits the expression of collagen type I in cells (IC
50 = 93 nM) and in mice when given orally at 10 mg/kg once a day. As TGF-β stimulates fibrosis in a range of tissues, GW 788388 reduces typical features of fibrosis, including tissue remodeling, increased expression of α-smooth muscle actin and production of collagen I. GW 788388 also blocks TGF-β-mediated production of VEGF by fibroblasts, as well as subsequent angiogenesis
in vitro. Inhibition of ALK5 signaling by GW 788388 also induces hypertrophy in femoral growth plates in rats.
References
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