BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity.
basic_science · Level V
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Abstract
Matrix metalloproteinases (MMPs) have been implicated in tumor cell invasion, metastasis, and angiogenesis. BAY 12-9566, a novel, non-peptidic biphenyl MMP inhibitor, has shown preclinical activity on a broad range of tumor models and is currently in clinical development. The purpose of this study was 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 = 8.4x10(-7) M), without affecting cell proliferation. In vivo, oral daily administration of BAY 12-9566 (50-200 mg/kg) inhibited angiogenesis induced by basic fibroblast growth factor in the Matrigel plug assay, reducing the hemoglobin content of the pellets. Histological analysis showed a reduction in the amount of functional vessels within the Matrigel. We conclude that the MMP inhibitor BAY 12-9566 inhibits angiogenesis, a property that further supports its clinical development as an antimetastatic agent.
Medical subject headings
- Angiogenesis Inhibitors
- Antineoplastic Agents
- Endothelium, Vascular
- Fibroblast Growth Factor 2
- Matrix Metalloproteinase Inhibitors
- Neovascularization, Pathologic
- Neovascularization, Physiologic
- Organic Chemicals