Method for determining the therapeutic activity of metalloproteinase inhibitor compounds

A method for determining the therapeutic potential of a peptidomimetic compound as an inhibitor of zinc-dependent metalloproteinase activity associated with pathological conditions of humans and animals, comprising the steps of:

• (a) conducting a first enzyme inhibition test and determining a first level of inhibitory activity of peptidomimetic compounds as inhibitors of a zinc-dependent metalloproteinase extracted from the venom of snakes belonging to the families Crotalidae and Viperidae;
• (b) screening said compounds on the basis of said first level of inhibitory activity by assessing whether each of said compounds has an inhibitory activity on said zinc-dependent metalloproteinase from snake venom expressed in terms of an IC.sub.50 not greater than 10.sup.-5 M;
• (c) conducting a second enzyme inhibition test and determining a second level of inhibitory activity of said compounds as inhibitors of zinc-dependent metalloproteinase endogenous in a mammal, the activity of said zinc-dependent metalloproteinase being associated with at least one pathological condition in said mammal;
• (d) screening said compounds on the basis of said second level of inhibitory activity by assessing whether each of said compounds has an inhibitory activity on said zinc-dependent metalloproteinase endogenous in mammals expressed in terms of an IC.sub.50 not greater than 10.sup.-5 M;
• whereby
• step (a) and step (b) make a primary selection of the tested compounds as inhibitors of zinc-dependent metalloproteinases form snake venom and therefore as potential inhibitors of zinc-dependent metalloproteinases in mammals;
• step (c) and step d) test the capability of said selected compounds for inhibiting the zinc-dependent metalloproteinases associated with at least one pathological condition in mammals, and
• the pharmacological activity against said at least one pathological condition of the compounds screened thereby is verified by pharmacological tests.