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

Martens, Erik; Leyssen, An; Aelst, Ilse Van; Fiten, Pierre; Piccard, Heléne; Hu, Jialiang; Descamps, Francis J; Steen, Philippe E. Van den; Proost, Paul; Damme, Jozef Van; Liuzzi, Grazia Maria; Riccio, P.; Polverini, Eugenia; Opdenakker, Ghislain

doi:10.1016/j.bbagen.2006.10.012

Cited by 85 publications

(61 citation statements)

References 36 publications

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“…The reasons for the failures of the above synthetic MMP inhibitors are not exactly understood, but it has been thought that they cover too wide a spectrum and so more selective MMP inhibitors are still required . In line with this idea, evidence is available suggesting that efforts to inhibit MMP activity should be directed at therapies exploiting endogenous MMP inhibitors, TIMPs (Ramirez-Correa et al, 2004;Zacchigna et al, 2004), or monoclonal antibodies against individual MMPs (Martens et al, 2007). Experiences from animal studies indicate that ADAMTS inhibitors are likely to have a position as future drugs.…”

Section: B Targeting the Degradation Of The Extracellular Matrixmentioning

confidence: 91%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

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Section: B Targeting the Degradation Of The Extracellular Matrixmentioning

confidence: 91%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

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“…The monoclonal antibodies REGA-3G12 and REGA-2D9 are specific to MMP-9 and do not cross react with MMP-2. MMP inhibition by REGA-3G12 does not appear to involve the zinc binding group or the fibronectin region, but instead binds to the catalytic domain [120]. REGA-1G8 is not as specific, and cross reacts with serum albumin.…”

Section: Mmp Inhibitors and Potential Benefits In Varicose Veinsmentioning

confidence: 98%

Matrix Metalloproteinases in Venous Tissue Remodeling and Varicose Vein Formation

Raffetto¹,

Khalil²

2008

CVP

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Matrix metalloproteinases (MMPs) play a major role in extracellular matrix (ECM) turnover under both physiological and pathological conditions. Studies on venous tissues from experimental animals and humans identified several MMP subtypes, and showed significant changes in the expression and activity of specific MMPs during vein wall remodeling. Also, significant research has focused on the role of MMPs in chronic venous disease (CVD) and varicose vein formation in the lower extremities and their progression to thrombophlebitis and venous leg ulcer. Several hypotheses have been forwarded regarding the pathophysiological mechanisms underlying the relation between MMPs and the formation, progression and complications of varicose veins. The effects of MMPs on ECM degradation could result in significant venous tissue remodeling and degenerative and structural changes in the vein wall, leading to venous dilation and valve dysfunction. MMPs may also induce early changes in the endothelium and venous smooth muscle function in the absence of significant ECM degradation or structural changes in the vein wall. In addition, evidence suggests increased activity of MMPs in the advanced stages of chronic venous insufficiency (CVI) associated with skin changes and leg ulceration as well as in the wound fluid environment. Several pharmacological therapies and surgical strategies are being utilized in the management of varicose veins, with variable success and recurrence rates. Inhibition of MMPs may represent a novel therapeutic intervention to limit the progression of varicose veins to CVI and leg ulceration.

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“…So far, this has been successful especially for MMP13-specific inhibitors [84]. Monoclonal antibodies against MMPs appear to be promising alternatives to synthetic inhibitors; an example is REGA-3G12, an antibody that selectively inhibits human MMP9 [85]. However, the difficulty of producing macromolecular proteins and the need for parenteral administration limit their therapeutic potential.…”

Section: Mmp Inhibitorsmentioning

confidence: 99%

A therapeutic role for matrix metalloproteinase inhibitors in lung diseases?

Vandenbroucke¹,

Dejonckheere²,

Libert³

2011

European Respiratory Journal

107

103

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Disruption of the balance between matrix metalloproteinases (MMPs) and their endogenous inhibitors is considered a key event in the development of pulmonary diseases such as chronic obstructive pulmonary disease, asthma, interstitial lung diseases and lung cancer. This imbalance often results in elevated net MMP activity, making MMP inhibition an attractive therapeutic strategy. Although promising results have been obtained, the lack of selective MMP inhibitors, together with limited knowledge regarding the exact functions of a particular MMP, hampers clinical application. This review discusses the involvement of different MMPs in lung disorders and future opportunities and limitations of therapeutic MMP inhibition.

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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

Cited by 85 publications

References 36 publications

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

Matrix Metalloproteinases in Venous Tissue Remodeling and Varicose Vein Formation

A therapeutic role for matrix metalloproteinase inhibitors in lung diseases?

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