Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor.
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.
Maekawa
R
R
Shionogi Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan.
Maki
H
H
Wada
T
T
Yoshida
H
H
Nishida-Nishimoto
K
K
Okamoto
H
H
Matsumoto
Y
Y
Tsuzuki
H
H
Yoshioka
T
T
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; C419963:N-alpha-(4-(2-phenyl-2H- tetrazole-5-yl) phenyl sulfonyl)-D-tryptophan; D013449:Sulfonamides