Synthetic urokinase inhibitors as potential anti-invasive drugs.
In carcinogenesis, proteinases play an important role in metastasis of solid malignant tumors. Aside from several matrix metalloproteinases and cathepsins, the urokinase-plasmin system seems to be one of the main players within the cell surface-associated proteolytic activity, facilitating tumor cell migration and invasion. Upon binding to a specific receptor, the enzymatic activity of urokinase is focused to the cell surface. The significance of the plasminogen activator system in malignancy is underlined by the finding of elevated levels of urokinase and its receptor in tumor tissues. Therefore, the possible use of urokinase inhibitors in the therapeutic treatment of cancer and metastasis has been the subject of intensive investigations. This review covers synthetic inhibitors of urokinase described up to December 2000, although the number of lead structures is still relatively small.
Zentrum für Vaskuläre Biologie und Medizin, Universität Jena, Nordhäuser Strasse 78, D-99089 Erfurt, Germany. stuerze@zmkh.ef.uni-jena.de
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J
Stürzebecher
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Schweinitz
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WA
Schmalix
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P
Wikström