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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1-2
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pubmed:dateCreated |
2008-3-3
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pubmed:abstractText |
CNTO 530 is a 58 kD antibody Fc domain fusion protein, created using Centocor's MIMETIBODY platform, that contains two EMP1 sequences as a pharmacophore. CNTO 530 has no sequence homology with EPO but acts as a novel erythropoietin receptor agonist. In UT-7(EPO) cells, CNTO 530 caused protein phosporylation of the erythropoietin receptor associated signaling pathway (Jak2, STAT5, AKT and ERK1/2). CNTO 530 also rescued these cells from apoptosis and mediated proliferation. In mice, pharmacokinetic analysis showed that CNTO 530 was slowly cleared from circulation with a t(1/2) approximately 40 h. Pharmacodynamic analysis in mice showed that a single sc dose of CNTO 530 caused a long-lived stimulation of erythropoiesis that translated into increases in red blood cell counts and hemoglobin values that were maintained for at least 28 d. In conclusion, CNTO 530 is a long-lived EPO-R agonist that stimulates erythropoiesis in a manner similar to epoetin-alpha. These data suggest that CNTO 530 may be an effective treatment of anemia in humans.
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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 |
Mar
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pubmed:issn |
0168-1656
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pubmed:author |
pubmed-author:AchuthanandamRR,
pubmed-author:BugelskiP JPJ,
pubmed-author:CapocasaleR JRJ,
pubmed-author:FisherP WPW,
pubmed-author:GradelFF,
pubmed-author:HuangCC,
pubmed-author:KELLYA TAT,
pubmed-author:KwokDD,
pubmed-author:LuJJ,
pubmed-author:MakropoulosDD,
pubmed-author:MarshallDD,
pubmed-author:NessporTT,
pubmed-author:Spinka-DomsTT,
pubmed-author:VolkAA
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
134
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
171-80
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18242752-Animals,
pubmed-meshheading:18242752-Antibodies, Monoclonal,
pubmed-meshheading:18242752-Apoptosis,
pubmed-meshheading:18242752-Biological Availability,
pubmed-meshheading:18242752-Bone Marrow,
pubmed-meshheading:18242752-Cell Line,
pubmed-meshheading:18242752-Cell Survival,
pubmed-meshheading:18242752-Female,
pubmed-meshheading:18242752-Flow Cytometry,
pubmed-meshheading:18242752-Humans,
pubmed-meshheading:18242752-Immunophenotyping,
pubmed-meshheading:18242752-Janus Kinase 2,
pubmed-meshheading:18242752-Mice,
pubmed-meshheading:18242752-Mice, Inbred C57BL,
pubmed-meshheading:18242752-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:18242752-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:18242752-Models, Biological,
pubmed-meshheading:18242752-Phosphorylation,
pubmed-meshheading:18242752-Receptors, Erythropoietin,
pubmed-meshheading:18242752-STAT5 Transcription Factor,
pubmed-meshheading:18242752-Signal Transduction
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pubmed:year |
2008
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pubmed:articleTitle |
CNTO 530: molecular pharmacology in human UT-7EPO cells and pharmacokinetics and pharmacodynamics in mice.
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pubmed:affiliation |
Centocor Research and Development, Radnor, PA 19087, United States. pbugelsk@cntus.jnj.com
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pubmed:publicationType |
Journal Article
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