Generation of Specific Matrix Metalloproteinase-9 Hemopexin Domain Inhibitors

Inhibitors that target a site on MMP-9’s hemopexin domain that are distinct and cannot be functionally substituted for one another. 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 Overview: 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. Development Stage: _In vivo_ CAM assay. Advantages: Target site selective

Does not inhibit the proteases catalytic function

No cross-reactivity to other MMPs. Applications: Cancer therapeutics. Intellectual Property Summary: Patent application submitted Stage of Development: US provisional application covering the composition of matter and method of use has been filed. Licensing Potential: Commercial partner,Development partner,Licensing Licensing Status: Available for License. Seeking interested partners to develop and commercialize the technology. #8910 Additional Information: novel inhibitor,matrix,matrix metalloproteinase,metalloproteinase,anti-cancer,cancer,drug development,drug target,inhibit,angiogenesis,metastatic,protease,mmp inhibition,mmp inhibitor,anticancer,cancer drugs,oncology drug,cancer metastasis,metastasis,cancer target,cancer targets,tumor cell,tumour cell,drug design,oncology therapeutic,oncology therapy,cancer therapeutic,cancer therapies,cancer therapy,anti-metastasis,collagenase,inhibitors,domain,evidence,catalytic,off-target,binding,assays,therapeutics Please note, header image is purely illustrative. Source: Emw, wikimedia commons, CC BY-SA 3.0.

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