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

Carmen Gatto, Monica Rieppi, Patrizia Borsotti, Silvia Innocenti, Roberta Ceruti, Teresa Drudis, Eugenio Scanziani, Anna M. Casazza, Giulia Taraboletti, Raffaella Giavazzi

Research output: Contribution to journalArticle

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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 = 8.4 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.

Original languageEnglish
Pages (from-to)3603-3607
Number of pages5
JournalClinical Cancer Research
Volume5
Issue number11
Publication statusPublished - Nov 1999

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Matrix Metalloproteinase Inhibitors
Fibroblast Growth Factor 2
Matrix Metalloproteinases
Inhibitory Concentration 50
Oral Administration
Neoplasms
Hemoglobins
Endothelial Cells
Cell Proliferation
Neoplasm Metastasis
matrigel
diphenyl
In Vitro Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gatto, C., Rieppi, M., Borsotti, P., Innocenti, S., Ceruti, R., Drudis, T., ... Giavazzi, R. (1999). BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity. Clinical Cancer Research, 5(11), 3603-3607.

BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity. / Gatto, Carmen; Rieppi, Monica; Borsotti, Patrizia; Innocenti, Silvia; Ceruti, Roberta; Drudis, Teresa; Scanziani, Eugenio; Casazza, Anna M.; Taraboletti, Giulia; Giavazzi, Raffaella.

In: Clinical Cancer Research, Vol. 5, No. 11, 11.1999, p. 3603-3607.

Research output: Contribution to journalArticle

Gatto, C, Rieppi, M, Borsotti, P, Innocenti, S, Ceruti, R, Drudis, T, Scanziani, E, Casazza, AM, Taraboletti, G & Giavazzi, R 1999, 'BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity', Clinical Cancer Research, vol. 5, no. 11, pp. 3603-3607.
Gatto C, Rieppi M, Borsotti P, Innocenti S, Ceruti R, Drudis T et al. BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity. Clinical Cancer Research. 1999 Nov;5(11):3603-3607.
Gatto, Carmen ; Rieppi, Monica ; Borsotti, Patrizia ; Innocenti, Silvia ; Ceruti, Roberta ; Drudis, Teresa ; Scanziani, Eugenio ; Casazza, Anna M. ; Taraboletti, Giulia ; Giavazzi, Raffaella. / BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity. In: Clinical Cancer Research. 1999 ; Vol. 5, No. 11. pp. 3603-3607.
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