LY-364947 (396129-53-6) is a selective ALK5 inhibitor, IC50 = 59, 400 and 1400 nM for TGF-β RI, TGF-β RII and MLK-7K, respectively1. Inhibits Smad2 phosphorylation induced by TGF-β as well as fibronectin expression and MDA-MB-231 cell invasion2. LY-364947 abolishes resistance of glioblastoma-initiating cells to radiation3. Cell permeable.
1) Sawyer et al. (2003), Synthesis and activity of new aryl-and hetero-aryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain; J. Med. Chem., 46 3953
2) Shiou et al. (2006), Smad4-dependent regulation of urokinase plasminogen activator secretion and RNA stability associated with invasiveness by autocrine and paracrine transforming growth factor-beta; J. Biol. Chem., 281 33971
3) Hardee et al. (2012), Resistance of glioblastoma-initiating cells to radiation mediated by the tumor microenvironment can be abolished by inhibiting transforming growth factor-β; Cancer Res., 72 4119