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  • Title: Tumor selective effect of RS-1541 (palmitoyl-rhizoxin) in M5076 sarcoma and host tissues in vivo.
    Author: Tokui T, Maeda N, Kuroiwa C, Sasagawa K, Inoue T, Kawai K, Ikeda T, Komai T.
    Journal: Pharm Res; 1995 Mar; 12(3):370-5. PubMed ID: 7617523.
    Abstract:
    RS-1541 is a 13-O-palmitoyl derivative of rhizoxin, an inhibitor of tubulin polymerization. After intravenous administration of RS-1541 to mice bearing M5076 sarcoma, the maximal inhibitory effect of RS-1541 on DNA synthesis in the tumor was observed 24 h after administration, in agreement with the Cmax of rhizoxin produced from RS-1541, but not with the Cmax of RS-1541. The inhibitory effect after RS-1541 was much higher than that after rhizoxin itself. In the spleen, thymus and bone marrow, DNA synthesis was strongly inhibited by rhizoxin but not by RS-1541. After administration of RS-1541, no significant amounts of rhizoxin were detected in the tissues, except for the tumor. In acute toxicity tests, RS-1541 appeared to be less toxic than rhizoxin. These results indicate that RS-1541 possesses a high tumor-selective effect compared with rhizoxin, because of the selective production of rhizoxin in the tumor after administration of RS-1541.
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