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Target intelligence / Profile preview
Matrix metalloproteinase-2; Matrix metalloproteinase-9; Matrix metalloproteinase-13 (MMP-2; MMP-9; MMP-13)
- Target
- MMP-2; MMP-9; MMP-13
- Molecular classification
- Enzyme, Metalloproteinase, Matrix metalloproteinase family
01
Overview
Matrix metalloproteinase-2, -9, and -13 are zinc-dependent endopeptidases that degrade components of the extracellular matrix (ECM), such as collagen, gelatin, and fibronectin. These enzymes play essential roles in normal tissue remodeling, wound healing, angiogenesis, and immune response, but their dysregulation contributes to the pathogenesis of diseases including cancer progression, chronic inflammatory diseases, and tissue fibrosis. They are targets for therapeutic inhibition due to their role in enabling tumor invasion, metastasis, and tissue destruction, but pharmacological inhibition carries safety challenges due to the need for selectivity and preservation of physiological ECM turnover.
- Other names
- Gelatinase A72 kDa type IV collagenaseGelatinase B92 kDa type IV collagenaseCollagenase-3
02
Mechanism of action
Competitive or allosteric inhibition of the catalytic zinc site Monoclonal antibody-mediated inhibition Binding to and irreversibly blocking active sites, preventing ECM degradation
03
Biological functions
Extracellular matrix degradationTissue remodelingCell migrationWound healingMorphogenesisInflammationFibrosisApoptosis regulationImmune response
04
Disease associations
Cancer (tumor invasion, metastasis, particularly breast cancer, colorectal cancer, and bone metastases)Inflammation (e.g., inflammatory bowel disease, colitis)Fibrosis (e.g., pulmonary fibrosis, lung fibrosis)Cardiovascular disease (e.g., atheroma, aneurysm, hypertension)Neurodegenerative disease (some evidence)Infection (tissue injury associated with infection)
05
Safety considerations
Off-target toxicity due to lack of selectivity in early drugsImpairment of normal tissue repair and wound healingMusculoskeletal syndrome (joint and tendon toxicity) observed in trials with broad MMP inhibitorsRegulation by endogenous inhibitors is crucial, and excessive inhibition can result in adverse tissue remodeling and healing deficits
06
Interacting drugs
MMP inhibitory monoclonal antibodies (e.g., anti-MMP-9 antibody AB0046)
2 more in the full profile.
07
Biomarkers
MMP-2, MMP-9, and MMP-13 levels in plasma, serum, or tissue as biomarkers for cancer, metastasis, and inflammatory diseaseMMP-9 considered a prognostic marker in breast cancer and colorectal cancer, and MMP-13 in breast cancer bone metastasis
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