Bone metastases (BM) are the primary cause of morbidity and mortality of prostate cancer (PCa) and no effective therapy is currently available. Transforming growth factor (TGF)-β1 has been implicated in the pathophysi ology of PCa BM. TGF-t31 is a pleiotropic growth factor that regulates cellular proliferation, chemotaxis, cellular differentiation, immune response, and angiogenesis. TGF-β1 receptors are transmembrane serine/threonine kinases. Upon TGF-β1 binding the type II receptor associates with and phosphorylates the type I receptor to initiate signaling. In the present work we tested the antitumor efficacy of a selective TGFt31 receptor kinase inhibitor (LY2109761, Eli Lilly and Co) in preclinical models of PCa BM. For these studies we used two bone derived PCa cell lines, MDA PCa 2b and PC3 cells.