TY - JOUR
T1 - BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity
AU - Gatto, Carmen
AU - Rieppi, Monica
AU - Borsotti, Patrizia
AU - Innocenti, Silvia
AU - Ceruti, Roberta
AU - Drudis, Teresa
AU - Scanziani, Eugenio
AU - Casazza, Anna M.
AU - Taraboletti, Giulia
AU - Giavazzi, Raffaella
PY - 1999/11
Y1 - 1999/11
N2 - 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 = 8.4 x 10-7 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.
AB - 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 = 8.4 x 10-7 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.
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M3 - Article
C2 - 10589777
AN - SCOPUS:0032710567
SN - 1078-0432
VL - 5
SP - 3603
EP - 3607
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -