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CNTO 530: Molecular pharmacology in human UT-7EPO cells and pharmacokinetics and pharmacodynamics in mice

Paper ID Volume ID Publish Year Pages File Format Full-Text
24862 43541 2008 10 PDF Available
Title
CNTO 530: Molecular pharmacology in human UT-7EPO cells and pharmacokinetics and pharmacodynamics in mice
Abstract

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-7EPO 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 t½ ≈ 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-α. These data suggest that CNTO 530 may be an effective treatment of anemia in humans.

Keywords
Recombinant proteins; Fusion proteins; Therapeutic proteins; Cytometry; Erythropoiesis; Drug effects
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 134, Issues 1–2, 20 March 2008, Pages 171–180
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us