Development of novel molecular-targeted medicine against aminopeptidase

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This study was aimed to develop novel inhibitors of aminopeptidase N(APN) overexpressed on cancer cell membrane and to evaluate the suppressive effect on cancer cell growth and angiogenesis. A newly-synthesized compound 24F, one of hydroxamic acid derivatives, inhibited the activity of aminopeptidases expressed on HL60 cell membrane. This compound inhibited the growth and invasion of hepatoma cell lines. In addition, incubation of vascular endothelial cells with 24F was found to be effective for the suppression of the angiogenic phenomena such as migration and tube formation. Furthermore, a newly-synthesized bestatin derivative LYP also had the ability to inhibit cancer cell growth as well as migration and tube formation of vascular endothelial cells. These results suggest that newly-synthesized aminopeptidase inhibitors are effective as an anti-cancer agent for hepatoma via inhibition of cancer cell invasion and angiogenesis surrounding cancer tissue.