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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2007-3-29
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pubmed:abstractText |
In our continued efforts to search for potent and novel receptor tyrosine kinase (RTK) inhibitors as potential anticancer agents, we discovered, through a structure-based design, that 3-aminoindazole could serve as an efficient hinge-binding template for kinase inhibitors. By incorporating an N,N'-diaryl urea moiety at the C4-position of 3-aminodazole, a series of RTK inhibitors were generated, which potently inhibited the tyrosine kinase activity of the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor families. A number of compounds with potent oral activity were identified by utilizing an estradiol-induced mouse uterine edema model and an HT1080 human fibrosarcoma xenograft tumor model. In particular, compound 17p (ABT-869) was found to possess favorable pharmacokinetic profiles across different species and display significant tumor growth inhibition in multiple preclinical animal models.
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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 |
Apr
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:AhmedAsma AAA,
pubmed-author:AlbertDaniel HDH,
pubmed-author:BauchJoy LJL,
pubmed-author:BouskaJennifer JJJ,
pubmed-author:BousquetPeter FPF,
pubmed-author:CunhaGeorge AGA,
pubmed-author:DaiYujiaY,
pubmed-author:DavidsenSteven KSK,
pubmed-author:GlaserKeith BKB,
pubmed-author:GoyM FMF,
pubmed-author:HarrisChristopher MCM,
pubmed-author:HartandiKresnaK,
pubmed-author:HickmanDeanD,
pubmed-author:JiZhiqinZ,
pubmed-author:LiJunlingJ,
pubmed-author:MarcottePatrick APA,
pubmed-author:MarshKennan CKC,
pubmed-author:MartinRuth LRL,
pubmed-author:MichaelidesMichael RMR,
pubmed-author:MoskeyMaria DMD,
pubmed-author:OlsonAmanda MAM,
pubmed-author:OsterlingDonald JDJ,
pubmed-author:PeaseLori JLJ,
pubmed-author:ReuterDavid RDR,
pubmed-author:SoniNiru BNB,
pubmed-author:StewartKent DKD,
pubmed-author:StollVincent SVS,
pubmed-author:TapangPaulP
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1584-97
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17343372-Adenosine Triphosphate,
pubmed-meshheading:17343372-Administration, Oral,
pubmed-meshheading:17343372-Angiogenesis Inhibitors,
pubmed-meshheading:17343372-Animals,
pubmed-meshheading:17343372-Binding Sites,
pubmed-meshheading:17343372-Edema,
pubmed-meshheading:17343372-Estradiol,
pubmed-meshheading:17343372-Female,
pubmed-meshheading:17343372-Humans,
pubmed-meshheading:17343372-Hydrophobic and Hydrophilic Interactions,
pubmed-meshheading:17343372-Indazoles,
pubmed-meshheading:17343372-Male,
pubmed-meshheading:17343372-Mice,
pubmed-meshheading:17343372-Models, Molecular,
pubmed-meshheading:17343372-NIH 3T3 Cells,
pubmed-meshheading:17343372-Phenylurea Compounds,
pubmed-meshheading:17343372-Phosphorylation,
pubmed-meshheading:17343372-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:17343372-Structure-Activity Relationship,
pubmed-meshheading:17343372-Uterus,
pubmed-meshheading:17343372-Xenograft Model Antitumor Assays
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pubmed:year |
2007
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pubmed:articleTitle |
Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor tyrosine kinase inhibitor.
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pubmed:affiliation |
Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6100, USA. yujia.dai@abbott.com
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pubmed:publicationType |
Journal Article
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