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.
|Titolo:||BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity|
|Parole Chiave:||Laminin; Animals; Neovascularization, Physiologic; Organic Chemicals; Antineoplastic Agents; Dose-Response Relationship, Drug; Humans; Mice; Angiogenesis Inhibitors; Drug Combinations; Endothelium, Vascular; Collagen; Proteoglycans; Fibroblast Growth Factor 2; Matrix Metalloproteinases; Cells, Cultured; Umbilical Veins; Mice, Inbred C57BL; Neovascularization, Pathologic; Cell Division|
|Settore Scientifico Disciplinare:||Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria|
|Data di pubblicazione:||nov-1999|
|Appare nelle tipologie:||01 - Articolo su periodico|