In the field of immuno-oncology and biotherapeutic research, the identification of novel biomarkers and therapeutic targets is crucial. One such validated target is Matrix Metalloproteinase-9 (MMP-9) — a proteolytic enzyme that plays a central role in extracellular matrix remodeling and is increasingly associated with inflammation, cancer, cardiovascular, and neurodegenerative diseases.

To support cutting-edge research in this area, SYnAbs offers high-quality monoclonal antibodies against MMP-9, designed for research use only (RUO), providing researchers with powerful tools to explore MMP-9 function, mechanism, and inhibition strategies with high specificity and reproducibility.

MMP-9, also known as gelatinase B, is a zinc-dependent endopeptidase belonging to the matrix metalloproteinase (MMP) family. Its biological function is the degradation of ECM components such as type IV and V collagen, elastin, and gelatin, which are critical to maintaining tissue structure.

MMP-9 is secreted as an inactive zymogen (proMMP-9) and requires proteolytic cleavage for activation. Its enzymatic activity is tightly controlled by endogenous inhibitors such as TIMPs (Tissue Inhibitors of Metalloproteinases). However, dysregulation of MMP-9 leads to pathological tissue destruction, making it an attractive research target for drug development and diagnostic biomarker discovery.

MMP-9 in Normal Physiology:

• Wound Healing: Facilitates keratinocyte migration and ECM remodeling.

• Embryogenesis: Promotes tissue morphogenesis and cell migration during development.

• Immune Modulation: Supports leukocyte infiltration through ECM degradation in inflammatory processes.

MMP-9 in Pathological Conditions:

• Cancer: Overexpression contributes to tumor invasion, angiogenesis, and metastasis.

• Inflammation: Elevated in chronic inflammatory diseases like rheumatoid arthritis and IBD.

• Neurology: Implicated in neuroinflammation and blood-brain barrier disruption.

• Cardiology: Drives plaque instability in atherosclerosis and aneurysm formation.

Due to this multifaceted role, targeting MMP-9 is a key strategy in preclinical models of cancer, inflammation, and CNS disease.

Despite being a promising target, small molecule inhibitors of MMP-9 have largely failed in clinical development due to poor specificity, low solubility, and adverse off-target effects.

Drugs like Batimastat, Marimastat, and Prinomastat showed early promise but were halted in Phase 3 trials. One of the main challenges lies in the high structural homology across MMPs, leading to unintended inhibition of closely related enzymes like ADAMs.

Thus, more selective and biologically relevant approaches are essential for targeting MMP-9 in a therapeutic or experimental context.

Monoclonal antibodies (mAbs) offer target specificity, longer half-life, and lower toxicity compared to small molecules. Antibody-based MMP-9 inhibitors are engineered to bind precise epitopes without affecting other MMPs or zinc-dependent enzymes.

• REGA-3G12, developed by KU Leuven, is a murine monoclonal antibody that binds specifically to the catalytic domain of MMP-9 while avoiding the zinc-binding site, offering a model for selective inhibition.

• Gilead’s AB0041 and AB0046 further demonstrated isoform-specific inhibition, leading to the development of Andecaliximab (GS-5745) — a humanized antibody tested in Phase 3 trials.

While Andecaliximab was discontinued after negative clinical results in gastric cancer, its development underscores the viability and research value of monoclonal antibodies against MMP-9.

At SYnAbs, we specialize in the development and production of hybridoma-derived monoclonal antibodies targeting human proteins of clinical and research interest, including Matrix Metalloproteinase-9. Our anti-MMP-9 RUO antibodies have been validated for:

• Western blotting

• ELISA-based quantification

• Flow cytometry and functional assays

• In vitro MMP-9 inhibition screening

• In vivo injection (endotoxin free level)

With validated performance across multiple applications, SYnAbs antibodies empower researchers to decode the role of MMP-9 in health and disease — and to identify new pathways and mechanisms relevant to drug discovery.

• ✅ Specific to active MMP9 without cross-reactivity to pro-MMP9

• ✅ Validated for multiple research techniques

• ✅ Batch-to-batch consistency and scalable supply

• ✅ Cross-reactivity to human and mouse MMP9

1. Salo T, Mäkelä M, Kylmäniemi M, Autio-Harmainen H, Larjava H. Expression of matrix metalloproteinase-2 and -9 during early human wound healing. Lab Invest. 1994 Feb;70(2):176-82. PMID: 8139259.
2. Alexander CM, Hansell EJ, Behrendtsen O, Flannery ML, Kishnani NS, Hawkes SP, Werb Z. Expression and function of matrix metalloproteinases and their inhibitors at the maternal-embryonic boundary during mouse embryo implantation. Development. 1996 Jun;122(6):1723-36. doi: 10.1242/dev.122.6.1723. PMID: 8674412.
3. Bischof P, Martelli M, Campana A, Itoh Y, Ogata Y, Nagase H. Importance of matrix metalloproteinases in human trophoblast invasion. Early Pregnancy 1995;1:263e9.
4. Luchian, I.; Goriuc, A.; Sandu, D.; Covasa, M. The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes. Int. J. Mol.Sci. 2022, 23, 1806
5. Klein G, Vellenga E, Fraaije MW, et al. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit Rev Oncol Hematol 2004;50:87-100.
6. Baugh M, Perry M, Hollander A, Rhodridavies D, Cross S, Lobo A, Taylor C, Evans G. Matrix Metalloproteinase levels are elevated in inflammatory bowel disease. Gastroenterology 1999;117:814±822
7. Giannelli G, Erriquez R, Iannone F, Marinosci F, Lapadula G, Antonaci S. MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in patients with rheumatoid arthritis and psoriatic arthritis. Clin Exp Rheumatol. 2004 May-Jun;22(3):335-8. PMID: 15144129.
8. Singh D., Srivastava S.K., Chaudhuri T.K., Upadhyay G. Multifaceted role of matrix metalloproteinases (MMPs) Front. Mol. Biosci. 2015;2:19. doi: 10.3389/fmolb.2015.00019.
9. Galis Z. S., Sukhova G. K., Lark M. W., Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. The Journal of Clinical Investigation. 1994;94(6):2493–2503. doi: 10.1172/JCI117619.v
10. N. A. Bhowmick, E. G. Neilson and H. L. Moses: Stromal fibroblasts in cancer initiation and progression. Nature, 432(7015), 332-337 (2004) DOI: 10.1038/nature03096
11. R. Kalluri and M. Zeisberg: Fibroblasts in cancer. Nat Rev Cancer.
12. Erik Martens, An Leyssen, Ilse Van Aelst, Pierre Fiten, Helene Piccard, Jialiang Hu, Francis J. Descamps, Philippe E. Van den Steen, Paul Proost, Jo Van Damme, Grazia Maria Liuzzi, Paolo Riccio, Eugenia Polverini, Ghislain Opdenakker. A monoclonal antibody inhibits gelatinase B/MMP-9 by selective binding to part of the catalytic domain and not to the fibronectin or zinc binding domains, Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1770, Issue 2, 2007, Pages 178-186, ISSN 0304-4165.
13. Marshall DC, Lyman SK, McCauley S, Kovalenko M, Spangler R, Liu C, Lee M, O'Sullivan C, Barry-Hamilton V, Ghermazien H, Mikels-Vigdal A, Garcia CA, Jorgensen B, Velayo AC, Wang R, Adamkewicz JI, Smith V. Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer. PLoS One. 2015 May 11;10(5):e0127063. doi: 10.1371/journal.pone.0127063. PMID: 25961845; PMCID: PMC4427291.