| Identification | Back Directory | [Name]
Filgrastim(granulocytecolony) | [CAS]
143011-72-7 | [Synonyms]
Filgrastim(granulocytecolony)
Granulocyte colony-stimulating factor
Human recombinant granulocyte colony stimulating factor |
| Questions And Answer | Back Directory | [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. | [Agonists and Antagonists]
Filgrastim produced by E. coli attached an additional
N-terminal methionine, and lenograstim produced by
CHO cells attached a single O-glycan; these were developed as therapeutic biologicals. Other molecules, including pegylated filgrastim, follow as next-generation
therapeutic reagents. The fusion proteins of G-CSF with
IgG1-Fc and IgG4-Fc are reported.
An antagonistic compound specific to G-CSF-G-CSFR
signaling has not been reported yet. | [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 |
| Hazard Information | Back Directory | [Description]
Granulocyte colony-stimulating factor is the primary regulator of proliferation and differentiation, maturation, survival, and functions of neutrophils/
granulocytes to exert biological defense mechanisms via neutrophil progenitors in the bone marrow. The bone marrow colony-forming activity of maturing
granulocytes was recognized in various cell and tissue cultures. Murine G-CSF was first purified from a lungconditioned medium from mice injected with bacterial
endotoxin. The human G-CSF was purified from the conditioned media of tumor cell lines, and the cDNA was independently cloned in 1986 by two groups. | [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. |
|
| Company Name: |
LGM Pharma
|
| Tel: |
1-(800)-881-8210 |
| Website: |
www.lgmpharma.com |
| Company Name: |
Sigma-Aldrich
|
| Tel: |
021-61415566 800-8193336 |
| Website: |
https://www.sigmaaldrich.cn |
| Company Name: |
TOSUN PHARM
|
| Tel: |
020-61855200 13326451905 |
| Website: |
www.toref.cn/ |
| Company Name: |
CarboMer, Inc.
|
| Tel: |
858 552 0992 |
| Website: |
www.carbomer.com |
|