We previously reported that 1-methyl-3-propy1-7-butylxantlaine (MPBX), a novel xanthine derivative, enhanced the antitumor activity of doxorubicin (DOX) due to inhibition of the DOX efflux from tumor cells. In this study, we investigated the effects of MPBX not only on drug sensitive tumor but also on multidrug resistant or metastatic tumors with the aim of developing its clinical use. In Ehrlich carcinoma bearing mice, MPBX enhanced antitumor activity of DOX 1.8-fold and increased the DOX concentration in the tumor 1.6-fold. Moreover, on multidrug resistant P388 leukemia (P388/DOX), DOX + MPBX significantly reduced the tumor weight to 48% of control level, whereas DOX alone did not reduce the tumor weight. MPBX increased the DOX influx into P388/DOX cells and inhibited the DOX efflux in vitro, supporting the increase in the DOX concentration in the tumor induced by MPBX in vivo. Furthermore, MPBX enhanced the therapeutic efficacy of pirarubicin, an anthracycline antibiotic, against metastatic M5076 sarcoma. In conclusion, MPBX enhanced the antitumor activity of anthracycline agents on sensitive, multidrug resistant or metastatic tumors. Thus, we expected that MPBX would be used as a biochemical modulator in clinical cancer chemothrapy.