Naphthofluorescein

HIF

-20

Naphthofluorescein (Naphthafluorescein) is a Mint3 inhibitor with potential antitumor and anti-inflammatory activities, inhibits the interaction between HIF-1 and Mint3, inhibits Mint3-dependent HIF-1 activity, and inhibits glycolytic activity in cancer cells and macrophages without showing significant in vitro cytotoxicity or in vivo side effects. Naphthofluorescein is also a fluorescent pH-sensitive probe for functional Cherenkov imaging.

Furin is a proprotein convertase, converting precursor proteins to functional proteins within the Golgi/trans-Golgi secretory pathway. Naphthofluorescein is a cell-permeable inhibitor of furin (IC50 = 12 μM). It inhibits furin-mediated cleavage of the pro-form of membrane type-1 matrix metalloproteinase (MT1-MMP), resulting in decreased levels of active MT1-MMP. This, in turn, suppresses MMP-2 activation and reduces cell motility in CHO cells expressing proMT1-MMP. Napthofluorescein significantly inhibits the invasion of Matrigel by the human fibrosarcoma cell line, HT1080. The effects of this furin inhibitor on other furin-mediated processes, in vivo or in vitro, remain to be determined.