1-Methyl-3-propyl-7-butylxanthine, a novel biochemical modulator, enhances therapeutic efficacy of adriamycin

Japanese Journal of Cancer Research : Gann
Y SadzukaK Miyamoto

Abstract

We have screened xanthine derivatives for activity as novel biochemical modulators by assay of their inhibitory effect on adriamycin efflux from tumor cells. Strong inhibition of adriamycin efflux was shown by some xanthine derivatives with various alkyl or oxoalkyl substituents at the 1-, 3- and 7-positions. 1-Methyl-3-propyl-7-butylxanthine (XT-77), which had the greatest inhibitory effect on adriamycin efflux in vitro among the compounds tested, potentiated adriamycin-induced antitumor activity by causing an increase of adriamycin concentration in the tumor in vitro. Furthermore, XT-77 reduced the adverse drug reactions of adriamycin by decreasing the adriamycin concentrations in the heart and the liver. Thus, the combination of XT-77 with adriamycin not only increased the antitumor activity of adriamycin, but also decreased the adverse drug reactions.

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Citations

Apr 28, 2004·Toxicology Letters·Yasuyuki SadzukaKen-Ichi Miyamoto
Dec 14, 2001·Journal of Medicinal Chemistry·M B LylesH R Rawls

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