|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
12
|
|
pubmed:dateCreated |
2000-7-24
|
|
pubmed:abstractText |
The sprouting of new blood vessels, or angiogenesis, is necessary for any solid tumor to grow large enough to cause life-threatening disease. Vascular endothelial growth factor (VEGF) is one of the key promoters of tumor induced angiogenesis. VEGF receptors, the tyrosine kinases Flt-1 and KDR, are expressed on vascular endothelial cells and initiate angiogenesis upon activation by VEGF. 1-Anilino-(4-pyridylmethyl)-phthalazines, such as CGP 79787D (or PTK787 / ZK222584), reversibly inhibit Flt-1 and KDR with IC(50) values < 0.1 microM. CGP 79787D also blocks the VEGF-induced receptor autophosphorylation in CHO cells ectopically expressing the KDR receptor (ED(50) = 34 nM). Modification of the 1-anilino moiety afforded derivatives with higher selectivity for the VEGF receptor tyrosine kinases Flt-1 and KDR compared to the related receptor tyrosine kinases PDGF-R and c-Kit. Since these 1-anilino-(4-pyridylmethyl)phthalazines are orally well absorbed, these compounds qualify for further profiling and as candidates for clinical evaluation.
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Aniline Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Phthalazines,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vascular Endothelial...,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/vatalanib
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
0022-2623
|
|
pubmed:author |
pubmed-author:AcemogluFF,
pubmed-author:AltmannK HKH,
pubmed-author:BoltWW,
pubmed-author:BoteVV,
pubmed-author:BrüggenJJ,
pubmed-author:BuchdungerEE,
pubmed-author:CozensRR,
pubmed-author:EmmeneggerRR,
pubmed-author:FerrariSS,
pubmed-author:FreiJJ,
pubmed-author:FurerRR,
pubmed-author:HofmannFF,
pubmed-author:LässerLL,
pubmed-author:LangMM,
pubmed-author:ManleyP WPW,
pubmed-author:Martiny-BaronGG,
pubmed-author:MassaSS,
pubmed-author:MestanJJ,
pubmed-author:RöselJJ,
pubmed-author:RothRR,
pubmed-author:SchlachterCC,
pubmed-author:SillsMM,
pubmed-author:StoverDD,
pubmed-author:TraxlerPP,
pubmed-author:VetterliWW,
pubmed-author:WietfeldBB
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
43
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2310-23
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:10882357-Administration, Oral,
pubmed-meshheading:10882357-Angiogenesis Inhibitors,
pubmed-meshheading:10882357-Aniline Compounds,
pubmed-meshheading:10882357-Animals,
pubmed-meshheading:10882357-Biological Availability,
pubmed-meshheading:10882357-CHO Cells,
pubmed-meshheading:10882357-Cell Line,
pubmed-meshheading:10882357-Cricetinae,
pubmed-meshheading:10882357-Enzyme Inhibitors,
pubmed-meshheading:10882357-Humans,
pubmed-meshheading:10882357-Mice,
pubmed-meshheading:10882357-Models, Molecular,
pubmed-meshheading:10882357-Neoplasms,
pubmed-meshheading:10882357-Neovascularization, Pathologic,
pubmed-meshheading:10882357-Phosphorylation,
pubmed-meshheading:10882357-Phthalazines,
pubmed-meshheading:10882357-Proto-Oncogene Proteins,
pubmed-meshheading:10882357-Pyridines,
pubmed-meshheading:10882357-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:10882357-Receptors, Growth Factor,
pubmed-meshheading:10882357-Receptors, Vascular Endothelial Growth Factor,
pubmed-meshheading:10882357-Structure-Activity Relationship,
pubmed-meshheading:10882357-Transfection,
pubmed-meshheading:10882357-Vascular Endothelial Growth Factor Receptor-1
|
|
pubmed:year |
2000
|
|
pubmed:articleTitle |
New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis.
|
|
pubmed:affiliation |
Oncology Research, and Process Research, NOVARTIS Pharma AG, CH-4002 Basel, Switzerland. guido.bold@pharma.novartis.com
|
|
pubmed:publicationType |
Journal Article
|
