Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor.

Abstract

The anti-metastatic efficacy and safety of a newly-developed matrix metalloproteinase (MMP) inhibitor were examined. MMI-166, a N-sulfonylamino acid derivative, inhibited the enzyme activity of MMP-2, 9, and 14 but not MMP-1, 3 or 7. Daily oral administration of MMI-166 resulted in potent inhibition of metastatic lung colonization of Lewis lung carcinoma injected via the tail vein and liver metastasis of C-1H human colon cancer implanted into the spleen at inhibition levels of 43% and 63%, respectively. Daily administration of MMI-166 also resulted in prolonged survival of mice given intraperitoneal implantation of Ma44 human lung cancer cells. The anti-metastatic activity of MMI-166 was as effective as that of other MMP inhibitors with broad inhibitory spectrum. MMI-166 did not affect in vitro tumor cell growth. Neither body weight losses nor hematotoxicity was observed during long-term treatment, indicating the safety of MMI-166 in mice. These results indicate that the selective MMP inhibitor MMI-166 has therapeutic potential as an anti-metastasis agent.

• Authors: R Maekawa, H Maki, T Wada, H Yoshida, K Nishida-Nishimoto, H Okamoto, Y Matsumoto, H Tsuzuki, T Yoshioka
• Journal: Clinical & experimental metastasis (Clin Exp Metastasis) Vol. 18 Issue 1 Pg. 61-6 ( 2000) ISSN: 0262-0898 [Print] Netherlands
• PMID: 11206840 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Enzyme Inhibitors
• Matrix Metalloproteinase Inhibitors
• N-alpha-(4-(2-phenyl-2H- tetrazole-5-yl) phenyl sulfonyl)-D-tryptophan
• Sulfonamides

Topics

• Animals
• Enzyme Inhibitors (pharmacology)
• Humans
• Matrix Metalloproteinase Inhibitors
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Neoplasm Metastasis (prevention & control)
• Sulfonamides (pharmacology)
• Tumor Cells, Cultured