TNP-470

A cell-permeable Fumagillin (Cat. No. 344845) analog that inhibits MetAP2, but not MetAP1, methionine aminopeptidase activity (IC₅₀ = 1 nM against human MetAP2) by covalently modifying MetAP2 active site histidine (aa 231 in human/mouse/rat; aa 174 in yeast) via its epoxide group, without affecting the inhibitory activity of MetAP2 against HRI- (heme-regulated inhibitor kinase) catalyzed eIF-2α phosphorylation. Cellular MetAP2 inhibition is particularly effective in inducing endothelial cytostasis (IC_{50 = 25 pM and 37 pM, respectively, against HUVEC and bovine BAEC proliferation by TNP-470), making TNP-470 a potent anti-angiogenesis agent in vivo (2 to 100 mg/kg in mice and rats; s.c.). Reported to be more potent and less toxic than Fumagillin.}

A cell-permeable Fumagillin (Cat. No. 344845) analog that inhibits MetAP2, but not MetAP1, methionine aminopeptidase activity (IC₅₀ = 1 nM against human MetAP2), without affecting the inhibitory activity of MetAP2 against HRI- (heme-regulated inhibitor kinase) catalyzed eIF-2α phosphorylation. A potent endothelial cytostasis inducer (IC₅₀ = 25 pM and 37 pM, respectively, against HUVEC and bovine BAEC) in vitro and an effective anti-angiogenesis agent in vivo (2 to 100 mg/kg in mice and rats; s.c.).

Toxicity: Irritant (B)

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Kusaka, M., et al. 1991. Biochem. Biophys. Res. Commun.174, 1070.
Ingber, D., et al. 1990. Nature348, 555.

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