143011-72-7

Basic information

• Product Name: Filgrastim(granulocytecolony)
• Synonyms: Filgrastim(granulocytecolony);Human recombinant granulocyte colony stimulating factor;Granulocyte colony-stimulating factor
• CAS NO: 143011-72-7
• Molecular Weight: 0
• Mol File: 143011-72-7.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• CAS DataBase Reference: Filgrastim(granulocytecolony)(CAS DataBase Reference)
• NIST Chemistry Reference: Filgrastim(granulocytecolony)(143011-72-7)
• EPA Substance Registry System: Filgrastim(granulocytecolony)(143011-72-7)

Safety Data

• Hazardous Substances Data: 143011-72-7(Hazardous Substances Data)

Usage

Description

Filgrastim (granulocyte colony-stimulating factor) is a glycoprotein that primarily regulates the proliferation, differentiation, maturation, survival, and functions of neutrophils/granulocytes. It plays a crucial role in the bone marrow colony-forming activity of maturing granulocytes and is involved in biological defense mechanisms via neutrophil progenitors.

Uses

Used in Pharmaceutical Industry:
Filgrastim is used as a therapeutic biological for stimulating the bone marrow to produce more neutrophils. It is particularly useful in treating patients with neutropenia, a condition characterized by an abnormally low number of neutrophils, which can result from chemotherapy, radiation therapy, or certain medical conditions.
Used in Oncology:
Filgrastim is used as a supportive care agent in cancer treatment to reduce the risk of infection and complications associated with neutropenia. It helps to increase the number of neutrophils, which are essential for fighting infections, in patients undergoing chemotherapy or radiation therapy.
Used in Hematology:
Filgrastim is used as a growth factor in hematology to stimulate the production of neutrophils in patients with various hematological disorders, such as myelodysplastic syndromes and aplastic anemia.
Used in Research and Development:
Filgrastim is used as a research tool in the development of next-generation therapeutic reagents, such as pegylated filgrastim and fusion proteins of G-CSF with IgG1-Fc and IgG4-Fc. These novel agents aim to improve the efficacy and duration of action of filgrastim in various clinical applications.

Properties

Mr. of human G-CSF is 18,671 (calculated polypeptide backbone) and 18–19 kDa on SDS-PAGE (O-glycosylated form secreted from tumor cell lines). The pI varies from 5 to 6 depending on O-glycosylation. The nonglycosylated form produced by E. coli retains biological activity.

Synthesis and release

The expression of the G-CSF gene is regulated by pathogen-mediated transcriptional and posttranscriptional pathways. Inflammatory factors such as bacterial lipopolysaccharide, interleukin-1β, tumor necrosis factor α, IL-1, and IL-17 from Th17 cells induce G-CSF expression via intracellular signaling though NF-κB, C/EBPα, and C/EBPβ. The increase in the number of circulating neutrophils reduces the production of G-CSF in the bone marrow.

Biological functions

G-CSF stimulates the proliferation, differentiation, and survival of neutrophil precursors in the bone marrow to promote their maturation process. G-CSF exerts minimal direct effects on the production of hematopoietic cell types other than the neutrophil lineage, as obtained in white blood cell differentials during clinical trials. The G-CSF-G-CSFR signaling in mature neutrophils activates multiple effector functions in response to bacterial infections, such as superoxide anion generation, the release of arachidonic acid, and the production of leukocyte alkaline phosphatase and myeloperoxidase. Neurons of the CNS express both G-CSF and G-CSF-R, suggesting an autocrine neuroprotection system, as a nonhematopoietic function

Clinical Use

Recombinant G-CSF therapies by filgrastim and lenograstim have been established in several indications. Primarily, G-CSF is administered to patients with severe congenital or chronic neutropenia caused by a myeloid maturation arrest in the bone marrow. G-CSF is also applicable to therapy-induced neutropenia developed in cancer patients receiving myelosuppressive chemotherapy and bone marrow transplant and in patients with acute myeloid leukemia receiving induction or consolidation chemotherapy. In addition, G-CSF induces the release of hematopoietic stem and progenitor cells from the bone marrow into the peripheral blood. Therefore, G-CSF is used in transplantation therapy for the mobilization and isolation of peripheral hematopoietic stem cells. The stem cell mobilization by G-CSF is supported by multiple mechanisms, including proteolytic enzyme release, the modulation of adhesion molecules, and the activation of CXCR4 chemokine receptors. Recently, the nonhemopoietic role of G-CSF has been evaluated in clinical trials including spinal cord injury by the ability of G-CSF for neuroprotective and neuroregenerative actions.

Structure and conformation

The human G-CSF and its receptor (G-CSFR) form a 2:2 complex with a crossover interaction between the Ig-like domains of the G-CSFR and GCSF. The predominant form of mature human G-CSF consists of 174 aa reduces, internally two disulfide bridges (C36dC42 and C64dC74), and one O-glycan at T133. In the splicing variant, consisting of 177 aa residues with the insertion of V-S-E between L35 and C36, the biological activity decreases 10-fold due to the modification of the ligand-receptor conformation. The reason for the difference in the biological roles of the two forms has not yet been elucidated.