- POLYMER-CONJUGATED METAP2 INHIBITORS, AND THERAPEUTIC METHODS OF USE THEREOF
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One aspect of the invention provides polymer conjugated MetAP2 inhibitors. While not being bound by any particular theory, it is believed that coupling the MetAP2 inhibitory core via the linkers described herein provides compounds with superior efficacy to the parent small molecules and superior pharmacokinetic profiles. In one aspect of the invention, the polymer conjugated MetAP2 inhibitors are useful in methods of treating disease, comprising administering to a subject in need thereof a therapeutically effective amount of a polymer conjugated MetAP2 inhibitor.
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Paragraph 0228; 0229
(2017/09/25)
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- Chemical modification of fumagillin. I. 6-O-Acyl, 6-O-sulfonyl, 6-O-alkyl, and 6-O-(N-substituted-carbamoyl)fumagillols
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The hydroxy group of fumagillol (3), a degradation product of fumagillin (1), was acylated, sulfonylated, alkylated or carbamoylated, and the anti-angiogenic activity of the resulting products was examined. These compounds inhibited the angiogenesis induced by basic fibroblast growth factor in the rat corneal micropocket assay and the growth of vascular endothelial cells in vitro. Among them, compound 2 (AGM-1470) was found to show the most potent inhibitory effect on the growth of vascular endothelial cells and was selected from this series as a candidate for further development.
- Marui,Itoh,Kozai,Sudo,Kishimoto
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