PMID: 2501026Aug 15, 1989Paper

Comparative antitumor properties in rodents of irreversible inhibitors of L-ornithine decarboxylase, used as such or as prodrugs

Cancer Research
N Claverie, P S Mamont

Abstract

The antitumor properties of (E)-2-(fluoromethyl)dehydroornithine methyl ester (delta-MFMO-ME) and of (E)-2-(fluoromethyl)dehydroornithine ethyl ester (delta-MFMO-EE), the prodrugs of delta-MFMO, an irreversible inhibitor of mammalian L-ornithine decarboxylase (ODC) 14 times more potent than alpha-difluoromethylornithine (DFMO) and equipotent to (2R,5R)-6-heptyne-2,5-diamine (MAP) in vitro, have been investigated in L1210 leukemia- and Lewis lung carcinoma-bearing mice. The anticancer properties of these esters have been compared with those of DFMO and MAP as a function of the dose, the route of administration, and the stage of the lewis lung carcinoma development in mice. The two esters, administered i.p. shortly after cell inoculation at one-fifth the dose of DFMO, prolonged the survival of mice-bearing leukemia to the same extent as DFMO and MAP. When administered orally to leukemia-bearing mice the two esters were equipotent at prolonging survival. The methyl ester appears, however, to be slightly, but not significantly, more effective than the ethyl ester against leukemia when given i.p., maximum prolongation of the mice survival (79%) occurring at 0.5 g/kg methyl ester every 12 h. The two esters achieve at one-sixth to one...Continue Reading

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