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rdf:type |
|
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lifeskim:mentions |
umls-concept:C0042776,
umls-concept:C0205314,
umls-concept:C0205531,
umls-concept:C0220825,
umls-concept:C0226896,
umls-concept:C0442027,
umls-concept:C0679622,
umls-concept:C0935763,
umls-concept:C1150587,
umls-concept:C1152564,
umls-concept:C1280500,
umls-concept:C1334306,
umls-concept:C1367731,
umls-concept:C1527415,
umls-concept:C1705632
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pubmed:issue |
7
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pubmed:dateCreated |
2007-3-13
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|
pubmed:abstractText |
Screening of a focused library of TGF beta kinase inhibitors in the cellular HCV replicon model with luciferase read out yielded a number of low micromolar HCV inhibitors. Medicinal chemistry driven optimization resulted in the discovery of 4-[2-(5-bromo-2-fluoro-phenyl)pteridin-4-ylamino]-N-[3-(2- oxopyrrolidin-1-yl)propyl]nicotinamide 36 with a replicon EC(50) of 64nM, associated with a selective kinase inhibitory profile for human JNK kinases 2 and 3 as well as VEGFR-1, 2, and 3 kinases. Moreover, 36 showed an advantageous PK profile in mice. Experiments performed using different replicon constructs suggest that this series of kinase inhibitors might mediate their effect through the HCV non-structural protein 5A (NS5A).
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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 |
0960-894X
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pubmed:author |
|
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1843-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17289388-Animals,
pubmed-meshheading:17289388-Antiviral Agents,
pubmed-meshheading:17289388-Area Under Curve,
pubmed-meshheading:17289388-Cell Line,
pubmed-meshheading:17289388-Chemistry, Pharmaceutical,
pubmed-meshheading:17289388-Drug Design,
pubmed-meshheading:17289388-Enzyme Inhibitors,
pubmed-meshheading:17289388-Evaluation Studies as Topic,
pubmed-meshheading:17289388-Hepacivirus,
pubmed-meshheading:17289388-Humans,
pubmed-meshheading:17289388-Inhibitory Concentration 50,
pubmed-meshheading:17289388-MAP Kinase Kinase 4,
pubmed-meshheading:17289388-Male,
pubmed-meshheading:17289388-Mice,
pubmed-meshheading:17289388-Models, Chemical,
pubmed-meshheading:17289388-Molecular Conformation,
pubmed-meshheading:17289388-Vascular Endothelial Growth Factor Receptor-1,
pubmed-meshheading:17289388-Viral Nonstructural Proteins
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pubmed:year |
2007
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pubmed:articleTitle |
Evaluation of the anti-hepatitis C virus effect of novel potent, selective, and orally bioavailable JNK and VEGFR kinase inhibitors.
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pubmed:affiliation |
Tibotec BVBA, Gen. De Wittelaan L11 B3, B-2800 Mechelen, Belgium. praboiss@tibbe.jnj.com
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pubmed:publicationType |
Journal Article
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