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rdf:type |
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lifeskim:mentions |
umls-concept:C0021469,
umls-concept:C0032200,
umls-concept:C0078058,
umls-concept:C0302600,
umls-concept:C0567416,
umls-concept:C0597357,
umls-concept:C1167622,
umls-concept:C1256770,
umls-concept:C1326912,
umls-concept:C1533157,
umls-concept:C1883254
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pubmed:issue |
29
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pubmed:dateCreated |
2005-7-7
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pubmed:abstractText |
Angiogenesis depends on vascular endothelial growth factor (VEGF) for initiation and platelet-derived growth factor (PDGF) for maintenance of blood vessels. We have designed a targeted library of compounds from which we identified a novel molecule, GFB-204, that binds PDGF and VEGF, blocks binding of PDGF and VEGF to their receptors (200-500 nM) and subsequently inhibits PDGFR and Flk-1 tyrosine phosphorylation and stimulation of the protein kinases Erk1, Erk2 and Akt and the signal transducer and activator of transcription STAT3. GFB-204 is selective for PDGF and VEGF and does not inhibit EGF, IGF-1 and FGF stimulation of Erk1/2, Akt and STAT3. GFB-204 inhibits endothelial cell migration and capillary network formation in vitro. Finally, treatment of mice with GFB-204 suppresses human tumor growth and angiogenesis. Thus, inhibition of VEGF and PDGF receptor binding with a synthetic molecule results in potent inhibition of angiogenesis and tumorigenesis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0950-9232
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pubmed:author |
pubmed-author:BaldiniLauraL,
pubmed-author:BlaskovichMichelle AMA,
pubmed-author:CarieAdamA,
pubmed-author:CoppolaDomenicoD,
pubmed-author:EnnisEileenE,
pubmed-author:HamiltonAndrew DAD,
pubmed-author:JainRishi KRK,
pubmed-author:PaquetteSteveS,
pubmed-author:SebtiSaïd MSM,
pubmed-author:SunJiazhiJ,
pubmed-author:WangDe-AnDA
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
24
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pubmed:owner |
NLM
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|
pubmed:authorsComplete |
Y
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pubmed:pagination |
4701-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15897913-Animals,
pubmed-meshheading:15897913-Calixarenes,
pubmed-meshheading:15897913-Cell Movement,
pubmed-meshheading:15897913-Cell Transformation, Neoplastic,
pubmed-meshheading:15897913-Humans,
pubmed-meshheading:15897913-Mice,
pubmed-meshheading:15897913-Mice, Nude,
pubmed-meshheading:15897913-Neoplasms, Experimental,
pubmed-meshheading:15897913-Neovascularization, Pathologic,
pubmed-meshheading:15897913-Platelet-Derived Growth Factor,
pubmed-meshheading:15897913-Receptors, Platelet-Derived Growth Factor,
pubmed-meshheading:15897913-Receptors, Vascular Endothelial Growth Factor,
pubmed-meshheading:15897913-Transplantation, Heterologous,
pubmed-meshheading:15897913-Vascular Endothelial Growth Factor A
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pubmed:year |
2005
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pubmed:articleTitle |
Inhibiting angiogenesis and tumorigenesis by a synthetic molecule that blocks binding of both VEGF and PDGF to their receptors.
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pubmed:affiliation |
Drug Discovery Program, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, MRC-DRDIS, Tampa, FL 33612, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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