The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing MMP (e.g., MMP9, MMPl 3, MMP 14, MMP 19, or MMP26) gene expression.

The MMP inhibition can be selective inhibition, for example, selective inhibition of MMP-2, MMP-9, and/or MMP-14.

Accordingly, the compound of formula (I) can be used in treatment of disorders or diseases mediated by MMP-2, and/or MMP-8, and/or MMP-9, and/or MMP-12, and/or MMP- 13.

In the activation of pro-MMP-2 by MT1-MMP, it is essentially required to form complexes consisting of plural MT1-MMPs, in particular, an MT1-MMP homodimer.

The invention provides isolated MMP-2, MMP-9 and MT1-MMP selective substrate polypeptides or functional peptidomimetrics.

Described are methods for treating diseases by use of agents that selectively inhibit human metalloproteinases (MMP), such as MMP-9 and MMP-2, while optionally sparing MMP-1.

MT4-MMP (MMP-17) is a glycosylphosphatidyl inositol (GPI) anchored MMP produced by cancer cells that promotes tumor vascularization and metastases.

The anti-MMP-13 monoclonal antibody is prepared by using purified human pro-MMP-13.

A method whereby latent MMP-13 and active MMP-13 can be separately assayed with the use of an anti-MMP-13 monoclonal antibody.

The expression of a potent protease such as MMP-1, MMP-2, MMP-3 and plasmin was observed in a synovial membrane of an OA patient.

More particularly, the present invention provides a new class of heterobicyclic MMP- 13 inhibiting and MMP-3 inhibiting compounds, that exhibit an increased potency in relation to currently known MMP- 13 and MMP-3 inhibitors.

Novel MMP-2/MMP-9 inhibitors and methods of using them are provided.

As the human-origin protease, use can be made of MMP-3, MMP-7, etc.

The proteolytic enzyme preferably is a matrix metalloprotease, in particular MMP-2 or MMP-9.

More particularly, the present invention provides a new class of heterobicyclic MMP-3 and/or MMP-13 inhibiting compounds, that exhibit an increased potency and selectivity in relation to currently known MMP-13 and MMP-3 inhibitors.