Abstract
The fumagillin family of natural products inhibits angiogenesis through the irreversible inhibition of the type 2 methionine aminopeptidase (MetAP2). Herein is reported a novel fumagillin analogue named fumarranol. It is shown that, like fumagillin, fumarranol selectively inhibits MetAP2 and endothelial cell proliferation. It is also active in a mouse model of angiogenesis in vivo. Unlike TNP-470, fumarranol does not covalently bind to MetAP2. Fumarranol may serve as a lead for a new class of angiogenesis inhibitors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminopeptidases / antagonists & inhibitors
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Angiogenesis Inhibitors / chemical synthesis*
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology
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Animals
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Cattle
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Cell Proliferation / drug effects
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Cells, Cultured
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Collagen
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Crystallography, X-Ray
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Cyclohexanes
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Drug Combinations
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Endothelial Cells / cytology
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Endothelial Cells / drug effects
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Endothelium, Vascular / cytology
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Fatty Acids, Unsaturated / chemical synthesis*
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Fatty Acids, Unsaturated / chemistry
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Fatty Acids, Unsaturated / pharmacology
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Glycoproteins / antagonists & inhibitors
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Laminin
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Methionyl Aminopeptidases
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Mice
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Molecular Structure
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Proteoglycans
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Sesquiterpenes / chemical synthesis*
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Sesquiterpenes / chemistry
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Sesquiterpenes / pharmacology
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Structure-Activity Relationship
Substances
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Angiogenesis Inhibitors
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Cyclohexanes
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Drug Combinations
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Fatty Acids, Unsaturated
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Glycoproteins
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Laminin
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Proteoglycans
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Sesquiterpenes
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fumarranol
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matrigel
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fumagillin
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Collagen
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Aminopeptidases
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METAP2 protein, human
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Methionyl Aminopeptidases