Recombinant Human Erythropoietin

Specification

• Cat#: THP-0067
• Product Name: Recombinant Human Erythropoietin
• Description: The product is a growth factor produced in the kidneys that stimulates the production of red blood cells. It works by promoting the division and differentiation of committed erythroid progenitors in the bone marrow. It is a 165-amino acid erythropoiesis-stimulating glycoprotein produced in cell culture using recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human growth factor gene has been introduced. The product contains the identical amino acid sequence of isolated natural product and has the same biological activity as the endogenous the product.
• Sequences: APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR
• Species: Human
• Molecular Weight: 18396.1 Da
• Source: Mammalian cells
• Purity: >99% by SDS-Page and HPLC analysis
• Cas No: 11096-26-7
• Formula: C815H1317N233O241S5
• Endotoxin Level: <0.001 EU per 1 μg of the protein by the LAL method
• Biological Activity: 8000IU/0.8ml

Pharmaceutical Information

• Pharmaceutical Application: Erythropoietin
• Applications: Indicated in adult and paediatric patients for the: treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis.treatment of anemia due to zidovudine in patients with HIV-infection. treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy.reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery.
• Examples of Clinical Use: Anemia
• Pharmacodynamics: The product and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks. Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly. Epoetin alfa serves to restore the product deficiency in pathological and other clinical conditions where normal production of the product is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks. Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy.
• Mechanism of action: Erythropoietin or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways. The affinity (Kd) of EPO for its receptor on human cells is ∼100 to 200 pM. Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins. The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x. The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C-γ1.
• Affected organisms: Humans and other mammals
• Targets: Target 1. Erythropoietin receptor