Tumor selective effect of RS-1541 (palmitoyl-rhizoxin) in M5076 sarcoma and host tissues in vivo.

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.

• Authors: T Tokui, N Maeda, C Kuroiwa, K Sasagawa, T Inoue, K Kawai, T Ikeda, T Komai
• Journal: Pharmaceutical research (Pharm Res) Vol. 12 Issue 3 Pg. 370-5 (Mar 1995) ISSN: 0724-8741 [Print] United States
• PMID: 7617523 (Publication Type: Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• DNA, Neoplasm
• Lactones
• Macrolides
• palmitoyl rhizoxin
• rhizoxin
• Thymidine

Topics

• Animals
• Antibiotics, Antineoplastic (pharmacology, toxicity)
• DNA, Neoplasm (biosynthesis)
• Dose-Response Relationship, Drug
• Female
• Injections, Intravenous
• Lactones (pharmacology, toxicity)
• Macrolides
• Male
• Mice
• Sarcoma, Experimental (metabolism)
• Thymidine (metabolism)
• Time Factors