4xct
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN]] May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.<ref>PMID:1480034</ref> | [[http://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN]] May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.<ref>PMID:1480034</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Matrix metalloproteinases (MMPs) have been shown to be involved in tumor-induced angiogenesis. In particular, MMP-2, MMP-9 and MMP-14 have been reported to be crucial for tumor angiogenesis and the formation of metastasis, thus becoming attractive targets in cancer therapy. Here, we report our optimization effort to identify novel N-isopropoxy-arylsulfonamide hydroxamates with improved inhibitory activity toward MMP-2, MMP-9 and MMP-14 with respect to the previously discovered compound 1. A new series of hydroxamates was designed, synthesized and tested for their anti-angiogenic activity using in vitro assays with human umbilical vein endothelial cells (HUVECs). A nanomolar MMP-2, MMP-9 and MMP-14 inhibitor was identified, compound 3, able to potently inhibit angiogenesis in vitro and also in vivo in the matrigel sponge assay in mice. Finally, X-ray crystallographic and docking studies were conducted for compound 3 in order to investigate its binding mode to MMP-9 and MMP-14. | ||
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| + | N-O-Isopropyl Sulfonamido-Based Hydroxamates as Matrix Metalloproteinase Inhibitors: Hit Selection and in vivo Antiangiogenic Activity.,Nuti E, Cantelmo AR, Gallo C, Bruno A, Bassani B, Camodeca C, Tuccinardi T, Vera L, Orlandini E, Nencetti S, Stura EA, Martinelli A, Dive V, Albini A, Rossello A J Med Chem. 2015 Aug 11. PMID:26263024<ref>PMID:26263024</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
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| + | ==See Also== | ||
| + | *[[Matrix metalloproteinase|Matrix metalloproteinase]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 07:38, 26 August 2015
Crystal structure of a hydroxamate based inhibitor ARP101 (EN73) in complex with the MMP-9 catalytic domain.
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