BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity

Matrix metalloproteinases (MMPs) have been implicated in tumor cell invasio n, metastasis, and angiogenesis, BAY 12-9566, a novel, non-peptidic bipheny l MMP inhibitor, has shown preclinical activity on a broad range of tumor m odels and is currently in clinical development. The purpose of this study w as to investigate the antiangiogenic activity of BAY 12-9566, In vitro, BAY 12-9566 prevented matrix invasion by endothelial cells in a concentration- dependent manner (IC50 = 8.4 x 10(-7) M), without affecting cell proliferat ion, In vivo, oral daily administration of BAY 12-9566 (50-200 mg/kg) inhib ited angiogenesis induced by basic fibroblast growth factor in the Matrigel plug assay, reducing the hemoglobin content of the pellets. Histological a nalysis showed a reduction in the amount of functional vessels within the M atrigel, We conclude that the MMP inhibitor BAY 12-9566 inhibits angiogenes is, a property that further supports its clinical development as an antimet astatic agent.