Lipegfilgrastim, Pegylated GCSF

Specification

• Cat#: THP-0083
• Product Name: Lipegfilgrastim, Pegylated GCSF
• Description: The product is a pegylated, recombinant granulocyte colony-stimulating factor (G-CSF) that was synthetized using a highly site-specific glycoPEGylation technology. The product is a covalent conjugate of Filgrastim with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine. The average molecular mass of the product comprises 18,798 Da for Filgrastim, 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG.
• Sequences: MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
• Species: Human
• Molecular Weight: 39000.0 Da (glycoPEGylated, approximate)
• Purity: >99% by SDS-Page and HPLC analysis
• Cas No: 1117844-87-7
• Formula: C866H1372N226O258S9*(C2H4O)n
• Endotoxin Level: <0.001 EU per 1 μg by the LAL method
• Biological Activity: 6mg/vial

Pharmaceutical Information

• Pharmaceutical Application: Pegylated GCSF
• Applications: Indicated for the reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes).
• Examples of Clinical Use: Reduction in the duration of neutropenia and the incidence of febrile neutropenia
• Pharmacodynamics: Mimicking endogenous granulocyte colony-stimulating factors, the product enhances the number and function of circulating neutrophils by binding to endogenous G-CSF receptors. A small increase in monocyte and/or lymphocyte counts may also be observed. Following a single subcutaneous dose administration of 100 μg/kg, the product resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis. Due to structural similarity between the product and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules. However, the product showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim.
• Mechanism of action: Endogenous granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates neutrophil progenitors. It is produced mainly by monocytes, fibroblasts and endothelial cells to promote the development of neutrophils and increase their proliferation and maturation. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function. Via binding to to the human G-CSF receptors, Pegylated GCSF activates the receptor signalling pathway as a growth factor to stimulate proliferation of haematopoietic progenitor cells and their differentiation into mature cells, and promote subsequent release into the peripheral blood. This stimulatory effect of Pegylated GCSF may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells. The presence of the PEG moiety in Pegylated GCSF decreases the plasma clearance and extends the drug's terminal elimination half-life, allowing for less frequent dosing.
• Affected organisms: Not Available
• Targets: Target 1. Granulocyte colony-stimulating factor receptor