Background

Matrix Metalloproteinase-9 (MMP-9), a type IV collagenase, is linked to cancer progression and metastasis. Despite increased evidence of correlation between MMP-9 and tumor metastasis, no success has been achieved in exploiting MMP-9 as a drug target, predominantly due to the conserved nature of target site. The target site traditionally exploited in MMP-9, is its catalytic domain, which is known to be highly conserved across several MMPs and thus attempts to use inhibitors of this domain has resulted in off target effects in clinics. Therefore, exploitation of MMP-9 against cancer inevitably requires a paradigm shift to identify inhibitors that can bind to the less conserved, non-catalytic domains, thereby improving specificity and reducing off-target binding.

Technology

Researchers from the Department of Chemistry at Stony Brook University have identified and experimentally tested series of compounds that exhibit high MMP-9 specificity. These inhibitors target a site on MMP-9?s hemopexin (PEX) domain that are distinct in each MMPs and cannot be functionally substituted for one another. Furthermore, our inventors show that PEX domain targeting can inhibit angiogenesis and invasion, the two key determinants of tumor cell metastatic potential. In summary, these PEX inhibitors would offer a unique strategy for drug designing in cancer and would overcome the off-target effects associated with previous approaches.

Advantages

-Target site selective -Does not inhibit the proteases catalytic function -No cross-reactivity to other MMPs.

Application

Cancer therapeutics.