Source:http://linkedlifedata.com/resource/pubmed/id/19534723
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2009-8-24
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| pubmed:abstractText |
To evaluate the anti-angiogenic efficacy of CB-12181 [an azasugar derivative that has inhibitory actions against matrix metalloproteinases (MMPs) and tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE)], we investigated the suppressing ability on in vitro (tube formation by endothelial cells) and in vivo (retinal neovascularization on murine ischemia-induced proliferative retinopathy) models of angiogenesis. For in vitro analysis, a capillary-like tube formation model using human umbilical vein endothelial cells (HUVECs) and fibroblasts co-culture assay was employed. Tube formation of HUVECs was stimulated by vascular endothelial growth factor (VEGF) and incubated with different concentrations of CB-12181 (0.1-100 microM) for 11 days. For in vivo analysis, mice were exposed to 75% oxygen between postnatal days 7 and 12 (P7 to P12). Then, the mice were removed from the oxygen treatment and treated with CB-12181 (1, 15, or 50 mg/kg) by daily subcutaneous injection from the time of reintroduction to room air at P12 until P16. At P17, pathological and physiological angiogenesis was quantified using retinal flat-mounts visualized by fluorescent angiography. In the in vitro angiogenesis model, CB-12181 significantly suppressed VEGF-induced HUVEC tube formation. Furthermore, in the in vivo angiogenesis model, administration of CB-12181 significantly suppressed retinal neovascularization without any apparent side effects on physiological revascularization to the oxygen-induced obliteration area. These results suggest that CB-12181 might be useful in the treatment of various diseases that depend on pathologic angiogenesis, and especially valuable for the treatment of diabetic retinopathy and retinopathy of prematurity.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3,4,5-trihydroxy-1-(4'-phenoxybenzen...,
http://linkedlifedata.com/resource/pubmed/chemical/ADAM Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Isothiocyanates,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfones,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/isothiocyanic acid,
http://linkedlifedata.com/resource/pubmed/chemical/tumor necrosis factor-alpha...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
1875-5739
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
6
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
140-7
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| pubmed:meshHeading |
pubmed-meshheading:19534723-ADAM Proteins,
pubmed-meshheading:19534723-Angiogenesis Inhibitors,
pubmed-meshheading:19534723-Animals,
pubmed-meshheading:19534723-Animals, Newborn,
pubmed-meshheading:19534723-Cell Proliferation,
pubmed-meshheading:19534723-Cells, Cultured,
pubmed-meshheading:19534723-Disease Models, Animal,
pubmed-meshheading:19534723-Dose-Response Relationship, Drug,
pubmed-meshheading:19534723-Drug Interactions,
pubmed-meshheading:19534723-Endothelial Cells,
pubmed-meshheading:19534723-Enzyme Inhibitors,
pubmed-meshheading:19534723-Humans,
pubmed-meshheading:19534723-Hydroxamic Acids,
pubmed-meshheading:19534723-Ischemia,
pubmed-meshheading:19534723-Isothiocyanates,
pubmed-meshheading:19534723-Mice,
pubmed-meshheading:19534723-Mice, Inbred C57BL,
pubmed-meshheading:19534723-Retinal Neovascularization,
pubmed-meshheading:19534723-Sulfones,
pubmed-meshheading:19534723-Tumor Necrosis Factor-alpha,
pubmed-meshheading:19534723-Vascular Endothelial Growth Factor A
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| pubmed:year |
2009
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| pubmed:articleTitle |
CB-12181, a new azasugar-based matrix metalloproteinase/tumor necrosis factor-alpha converting enzyme inhibitor, inhibits vascular endothelial growth factor-induced angiogenesis in vitro and retinal neovascularization in vivo.
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| pubmed:affiliation |
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Mitahora-higashi, Gifu, Japan.
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| pubmed:publicationType |
Journal Article
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