Novel inhibitors of Matrix Metalloproteinase-9 (MMP-9) for anti-cancer drug development

Novel inhibitors of Matrix Metalloproteinase-9 (MMP-9) for anti-cancer drug development

BACKGROUND 

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.

DESCRIPTION 
Prof. Sampson and colleagues 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 l Does not inhibit the proteases catalytic function l No cross-reactivity to other MMPs

APPLICATION 

Cancer therapeutics

DEVELOPMENT STAGE 
In vivo CAM assay
PATENT STATUS 

A PCT application (PCT/US18/23676) covering the composition of matter and method of use is pending.

ADDITIONAL INFORMATION

INVENTORS 

Vincent Alford
Graduate Student

Anushree Kamath
Postdoc.

Jian Cao M.D.
Professor

Nicole Sampson Ph. D.
Professor and Interim Dean

Iwao Ojima Ph. D.
Distinguished Professor and Director

Xiaodong Ren
postdoc

CASE MANAGER 

Valery Matthys, Ph. D.
valery.matthys@stonybrook.edu
6316326561

LICENSING STATUS 

Available for License

LICENSING POTENTIAL 
Seeking interested partners to develop and commercialize the technology
TECHNOLOGY ID 
050-8910
PRIMARY KEY 
1891825
KEYWORDS 

MMP9 inhibitors l PEX domain inhibitors l anti-cancer l anti-metastatic l CAM assay

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