Tnp470

Several natural products have shown activity as angiogenesis inhibitors.47 The best studied, and one of the most potent angiostatic agents, is fumagillin, isolated from Aspergillus fumigatus and widely employed as an antifungal in Nosema apis infections in honeybees. Fumagillin is an inhibitor of methionine aminopeptidase-2,48 an enzyme involved in endothelial proliferation. It also inhibits the expression of the ETS1 transcription factor, which regulates the expression of VEGFs.49 Its toxicity prompted the preparation of analogs, and among them the most advanced one is TNP-470, which is being studied for several lymphomas, acute leukemias, and solid tumors. Because of neurotoxicity problems, conjugates of this compound have been developed in order to prevent its access through the blood-brain barrier.50

Fumagillin O O

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