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. 2011:2011:191670.
doi: 10.1155/2011/191670. Epub 2010 Oct 28.

New Strategies for the Next Generation of Matrix-Metalloproteinase Inhibitors: Selectively Targeting Membrane-Anchored MMPs with Therapeutic Antibodies

Laetitia Devy  1 , Daniel T Dransfield
Affiliations

New Strategies for the Next Generation of Matrix-Metalloproteinase Inhibitors: Selectively Targeting Membrane-Anchored MMPs with Therapeutic Antibodies

Laetitia Devy et al. Biochem Res Int. 2011.

Abstract

MMP intervention strategies have met with limited clinical success due to severe toxicities. In particular, treatment with broad-spectrum MMP-inhibitors (MMPIs) caused musculoskeletal pain and inflammation. Selectivity may be essential for realizing the clinical potential of MMPIs. Here we review discoveries pinpointing membrane-bound MMPs as mediators of mechanisms underlying cancer and inflammation and as possible therapeutic targets for prevention/treatment of these diseases. We discuss strategies to target these therapeutic proteases using highly selective inhibitory agents (i.e., human blocking antibodies) against individual membrane-bound MMPs.

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Figures

Figure 1
Figure 1
MMP inhibitor selection strategy.
Figure 2
Figure 2
Primary structure of membrane-anchored MMPs.
See this image and copyright information in PMC

References

    1. Zucker S, Cao J, Chen W-T. Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene. 2000;19(56):6642–6650. - PubMed
    1. Pei D, Kang T, Qi H. Cysteine array matrix metalloproteinase (CA-MMP)/MMP-23 is a type II transmembrane matrix metalloproteinase regulated by a single cleavage for both secretion and activation. Journal of Biological Chemistry. 2000;275(43):33988–33997. - PubMed
    1. Velasco G, Pendás AM, Fueyo A, Knäuper V, Murphy G, López-Otín C. Cloning and characterization of human MMP-23, a new matrix metalloproteinase predominantly expressed in reproductive tissues and lacking conserved domains in other family members. Journal of Biological Chemistry. 1999;274(8):4570–4576. - PubMed
    1. Levitt NC, Eskens FALM, O’Byrne KJ, et al. Phase I and pharmacological study of the oral matrix metalloproteinase inhibitor, MMI270 (CGS27023A), in patients with advanced solid cancer. Clinical Cancer Research. 2001;7(7):1912–1922. - PubMed
    1. Noe MC, Natarajan V, Snow SL, et al. Discovery of 3,3-dimethyl-5-hydroxypipecolic hydroxamate-based inhibitors of aggrecanase and MMP-13. Bioorganic and Medicinal Chemistry Letters. 2005;15(11):2808–2811. - PubMed

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