LY2109761

Description: LY2109761 (LY-2109761; LY 2109761) is a novel, orally bioavailable and selective dual inhibitor of transforming growth factor beta receptor I/II (TGF-beta receptor type I/II: TbetaRI/II) with potential antitumor activity. It inhibits TGF-beta receptor type I/II with Ki values of 38 nM and 300 nM in a cell-free assay, respectively; LY2109761 was shown to be able to negatively affect the phosphorylation of Smad2. In vivo, LY2109761, in combination with gemcitabine, significantly reduced the tumor burden, prolonged survival, and reduced spontaneous abdominal metastases. The efficacy of LY2109761 on tumor growth, survival, and reduction of spontaneous metastasis have been evaluated in an orthotopic murine model of metastatic pancreatic cancer expressing both luciferase and green fluorescence proteins.

References: Mol Cancer Ther. 2008 Apr; 7(4):829-40; Hepatology. 2008 May; 47(5):1557-66.