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SKI2162, an inhibitor of the TGF-? type I receptor (ALK5), inhibits radiation-induced fibrosis in mice.

ABSTRACT: Here we demonstrated that SKI2162, a small-molecule inhibitor of the TGF-? type I receptor (ALK5), prevented radiation-induced fibrosis (RIF) in mice. SKI2162 inhibited phosphorylation of Smad and induction of RIF-related genes in vitro. In RIF a mouse model, SKI2162 reduced late skin reactions and leg-contracture without jeopardizing the acute skin reaction. Irradiation of mouse tissue increased COL1A2 mRNA levels, and topical administration of SKI2162 significantly inhibited this effect. Thus, these findings support that SKI2162 has potential value as novel RIF-protective agent, and could be candidate for clinical trials.

SUBMITTER: Park JH

PROVIDER: S-EPMC4414180 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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SKI2162, an inhibitor of the TGF-β type I receptor (ALK5), inhibits radiation-induced fibrosis in mice.

Park Jin-hong JH Ryu Seung-Hee SH Choi Eun Kyung EK Ahn Seung Do SD Park Euisun E Choi Kyung-Chul KC Lee Sang-wook SW

Oncotarget 20150201 6

Here we demonstrated that SKI2162, a small-molecule inhibitor of the TGF-β type I receptor (ALK5), prevented radiation-induced fibrosis (RIF) in mice. SKI2162 inhibited phosphorylation of Smad and induction of RIF-related genes in vitro. In RIF a mouse model, SKI2162 reduced late skin reactions and leg-contracture without jeopardizing the acute skin reaction. Irradiation of mouse tissue increased COL1A2 mRNA levels, and topical administration of SKI2162 significantly inhibited this effect. Thus, ...[more]

PMID: 25686821

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