title: SKI2162, an inhibitor of the TGF-β type I receptor (ALK5), inhibits radiation-induced fibrosis in mice.
abstract: 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, these findings support that SKI2162 has potential value as novel RIF-protective agent, and could be candidate for clinical trials.
authors: Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors: Jin-hong
authors: JH
authors: Park
authors: Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors: Seung-Hee
authors: SH
authors: Ryu
authors: Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors: Eun Kyung
authors: EK
authors: Choi
authors: Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors: Seung Do
authors: SD
authors: Ahn
authors: Life Science Research Center, SK Chemicals, Seongnam-si, Korea.
authors: Euisun
authors: E
authors: Park
authors: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea.
authors: Kyung-Chul
authors: KC
authors: Choi
authors: Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors: Sang-wook
authors: SW
authors: Lee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005355:Fibrosis / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000532:radiotherapy; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000201:enzymology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011897:Random Allocation; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism
chemical_list: D011837:Radiation-Protective Agents; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse