Potent anti-angiogenic action of AGM-1470: comparison to the fumagillin parent.
The anti-angiogenic activity of AGM-1470, a new synthetic analog of fumagillin isolated from Aspergillus fumigatus, was extensively examined both in vitro and in vivo using four different types of assay and compared to that of the fumagillin parent. Locally administered AGM-1470 inhibited the angiogenesis in the chick embryo chorioallantoic membrane assay and the rat corneal assay. In the rat sponge implantation assay, systemically administered AGM-1470 inhibited angiogenesis induced by basic fibroblast growth factor. Furthermore, in the rat blood vessel organ culture assay, AGM-1470 (1-1,000 ng/ml) was found to selectively inhibit the capillary-like tube formation of endothelial cells with a minimal effect on the non-endothelial cell growth. AGM-1470 showed more potent anti-angiogenic activity and less toxicity than the fumagillin parent. Therefore, AGM-1470 is much better than the fumagillin parent as anti-angiogenic compound.
Kusaka
M
M
Biology Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Sudo
K
K
Fujita
T
T
Marui
S
S
Itoh
F
F
Ingber
D
D
Folkman
J
J
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009389:Neovascularization, Pathologic; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D009924:Organ Culture Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects / Q000502:physiology*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; C026211:fumagillin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol