Fumarranol, a rearranged fumagillin analogue that inhibits angiogenesis in vivo.
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.
Lu
Jun
J
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Chong
Curtis R
CR
Hu
Xiaoyi
X
Liu
Jun O
JO
D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D018360:Crystallography, X-Ray; D003510:Cyclohexanes; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D007797:Laminin; D063208:Methionyl Aminopeptidases; D051379:Mice; D015394:Molecular Structure; D011509:Proteoglycans; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D004338:Drug Combinations; D005231:Fatty Acids, Unsaturated; D006023:Glycoproteins; D007797:Laminin; D011509:Proteoglycans; D012717:Sesquiterpenes; C514166:fumarranol; C059485:matrigel; C026211:fumagillin; D003094:Collagen; D000626:Aminopeptidases; C081311:METAP2 protein, human; D063208:Methionyl Aminopeptidases