The State University of New York

The Research Foundation of Suny

Ctt Cancer Targeting Technologies Oy

Tuula A Salo

Lorne M Golub

Timo Arto Sorsa

Olli P Teronen

Nungavarm S Ramamurthy

Hsi-Ming Lee

Erkki Koivunen

Timo A Sorsa

The present invention relates to novel matrix metalloproteinase (MMP) inhibitors and down-regulators, to a process for the preparation of these inhibitors, to pharmaceutical compositions comprising these inhibitors/down-regulators, to the use of the novel MMP inhibitors for the manufacture of pharmaceutical and research preparations, to a method for inhibiting and down-regulating MMP-dependent conditions either in vivo or in vitro, to a method for inhibiting formation, synthesis, expression activations, and/or functions as well as actions of matrix metalloproteinases, and to the use of the novel MMP inhibitors and down-regulators in biochemical isolation and purification procedures of matrix metalloproteinases.

Matrix metalloproteinase inhibitors and down-regulators

The invention is a method of inhibiting the activity of membrane-type matrix metalloproteinase (MT-MMP) in biological systems. Accordingly, the invention permits the treatment of medical conditions in mammals that are characterized by MT-MMP activity, and especially those conditions characterized by excessive MT-MMP activity. The method employs a tetracycline compound, preferably a non-antimicrobial tetracycline, and more preferably 6-demethyl-6-deoxy-4-de(dimethylamino)tetracycline (CMT-,) or 6-&agr;-deoxy-5-hydroxy-4-de(dimethylamino)tetracycline (CMT-,) to inhibit the MT-MMP activity.

Method of inhibiting membrane-type matrix metalloproteinase

Tissue-destructive conditions related to excess protemase activity in a biological system are treated or prevented by administering to the system a composition which combines a tetracycline and a bisphosphonate in synergistic proteinase inhibiting amounts.

Combination of bisphosphonate and tetracycline

Tissue-destructive conditions related to excess proteinase activity in a biological system are treated or prevented by administering to the system a composition which combines a tetracycline and a bisphosphonate in synergistic proteinase inhibiting amounts.

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Oulu, Finland

Tuula A Salo