SKI2162, an inhibitor of the TGF-beta type I receptor (ALK5), inhibits radiation-induced fibrosis in mice.
MouseRadiationBALB/cMalen = Systemic study: saline n = 20, SKI2162 n = 21, pentoxifylli…Intraperitoneal for SKI2162 and pentoxifylline, oral for tocopherol, and topical application to the irradiated site10 mg/kg systemically; topical formulations of 0.1 per cent…Initiated immediately after irradiation
Model: Radiation-induced fibrosis of the left hind limb, delivered as two weekly 22 Gy fractions by linear accelerator; the topical experiment used a single 35 Gy dose
SKI2162 inhibited ALK5 with an IC50 of 0.094 micromolar and abolished TGF-beta1-induced Smad2 and Smad3 phosphorylation at 400 nanomolar. In mice it significantly reduced leg contracture from 6 to 16 weeks, lowered the 16-week late skin reaction score to 2.73 plus or minus 0.16 versus 3.14 plus or…
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