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rdf:type |
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lifeskim:mentions |
umls-concept:C0010592,
umls-concept:C0015272,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0205314,
umls-concept:C0243071,
umls-concept:C0369335,
umls-concept:C0679622,
umls-concept:C1328949,
umls-concept:C1533691,
umls-concept:C2742152
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pubmed:issue |
2
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pubmed:dateCreated |
2010-1-25
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pubmed:abstractText |
SCY-635 is a novel nonimmunosuppressive cyclosporine-based analog that exhibits potent suppression of hepatitis C virus (HCV) replication in vitro. SCY-635 inhibited the peptidyl prolyl isomerase activity of cyclophilin A at nanomolar concentrations but showed no detectable inhibition of calcineurin phosphatase activity at concentrations up to 2 microM. Metabolic studies indicated that SCY-635 did not induce the major cytochrome P450 enzymes 1A2, 2B6, and 3A4. SCY-635 was a weak inhibitor and a poor substrate for P-glycoprotein. Functional assays with stimulated Jurkat cells and stimulated human peripheral blood mononuclear cells indicated that SCY-635 is a weaker inhibitor of interleukin-2 secretion than cyclosporine. A series of two-drug combination studies was performed in vitro. SCY-635 exhibited synergistic antiviral activity with alpha interferon 2b and additive antiviral activity with ribavirin. SCY-635 was shown to be orally bioavailable in multiple animal species and produced blood and liver concentrations of parent drug that exceeded the 50% effective dose determined in the bicistronic con1b-derived replicon assay. These results suggest that SCY-635 warrants further investigation as a novel therapeutic agent for the treatment of individuals who are chronically infected with HCV.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-12065751,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-12324553,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-14578868,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-14583619,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-14688826,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-14988824,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-14996676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-15057920,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-15450954,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-15521004,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-15620875,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-16107837,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-16314065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-16557546,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-16940091,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-17130250,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-17919644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-18023036,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-18302285,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-18385230,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-18798336,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-19380579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-2492638,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-4980133,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-7884893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-7957535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933795-8045510
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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 |
Feb
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pubmed:issn |
1098-6596
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
54
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
660-72
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pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
pubmed-meshheading:19933795-Animals,
pubmed-meshheading:19933795-Antiviral Agents,
pubmed-meshheading:19933795-Cell Line,
pubmed-meshheading:19933795-Cells, Cultured,
pubmed-meshheading:19933795-Cyclophilin A,
pubmed-meshheading:19933795-Cyclosporins,
pubmed-meshheading:19933795-Dogs,
pubmed-meshheading:19933795-Dose-Response Relationship, Drug,
pubmed-meshheading:19933795-Enzyme Activation,
pubmed-meshheading:19933795-Haplorhini,
pubmed-meshheading:19933795-Hepacivirus,
pubmed-meshheading:19933795-Hepatitis C,
pubmed-meshheading:19933795-Hepatocytes,
pubmed-meshheading:19933795-Humans,
pubmed-meshheading:19933795-Immunosuppressive Agents,
pubmed-meshheading:19933795-Interleukin-2,
pubmed-meshheading:19933795-Jurkat Cells,
pubmed-meshheading:19933795-Leukocytes, Mononuclear,
pubmed-meshheading:19933795-Mice,
pubmed-meshheading:19933795-Molecular Structure,
pubmed-meshheading:19933795-RNA, Viral,
pubmed-meshheading:19933795-Rats,
pubmed-meshheading:19933795-Virus Replication
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pubmed:year |
2010
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pubmed:articleTitle |
SCY-635, a novel nonimmunosuppressive analog of cyclosporine that exhibits potent inhibition of hepatitis C virus RNA replication in vitro.
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pubmed:affiliation |
Scynexis, Inc., 3501C Tricenter Boulevard, Durham, NC 27713, USA. Sam.Hopkins@scynexis.com
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pubmed:publicationType |
Journal Article
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