Ancestim
Ancestim Uses, Dosage, Side Effects, Food Interaction and all others data.
Ancestim is a non-glycosylated recombinant methionyl human stem cell factor. It is a 166 amino acid protein produced by E. coli with an amino acid sequence that is identical to the natural sequence predicted from human DNA sequence analysis, except for the addition of an N-terminal methionine. Ancestim was developed by Amgen and sold to Biovitrium in December 2008. It was submitted to the FDA under the status of recommendation for approval with a 10 to 1 votes. It was also approved by Health Canada in 1999 but it is currently under the status of canceled post-market.
Ancestim action on hemotopeitic progenitor cells stimulates its proliferation, differentiation, commitment and functional activation. This stimulation results in an increase on circulating peripheral blood progenitor cells like CD34, granulocyte macrophage colony-forming units and erythroid burst-forming units.
| Trade Name | Ancestim |
| Generic | Ancestim |
| Ancestim Other Names | Ancestim |
| Type | |
| Formula | C1662H2650N422O512S18 |
| Weight | 18540.0 Da (non-glycosylated) |
| Groups | Approved, Investigational, Withdrawn |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Ancestim is a human stem cell factor used in combination with filgrastim during autologous peripheral blood progenitor cell (PBPC) transplantation to increase PBPC mobilization for improved collection.
Ancestim, in combination with filgrastim, is indicated for the setting of autologous peripheral blood progenitor cell transplantation in patients at risk of poor peripheral blood progenitor cell mobilisation. The use of ancestim with filgrastim will generate a sustained increase in the number of peripheral blood progenitor cells capable of engraftment. It is used for mobilization of progenitor cells from the bone marrow to the peripheral blood with or withouth mobilizing chemotherapy. The harvested progenitor cells can be used for transplant following myelosuppressive or myeloablative therapies.
How Ancestim works
Ancestim alone is unable to increase peripheral blood progenitor cells so it has to be administered with filgastrim, a granulocyte colony-stimulating factor. Ancestrim will bind to the c-KIT expressed in hemocytoblasts, myeloid progenitors, megakaryocytes, immature mast cells, myeloblasts and lymphoid progenitors. Ancestim binding will cause receptor homodimerization and autophosphorylation at tyrosine residues. The activation of this receptor leads to the activation of a signaling cascade that contains the RAS/ERK, PI3-Kinase, Src kinase and JAK/STAT pathways which will later stimulate proliferation, differentiation and activation of the cell lines.
Toxicity
Ancestim was not genotoxic for gene mutation or chromosomal damage and it did not have any effect in fertility.
Volume of Distribution
Preclinical reports demonstrate that after intravenous administration of ancestim, the distribution profile is primarily in plasma and kidneys with a subsequent and rapid loss from all tissues.
Elimination Route
The pharmacokinetics of ancestim has a dose-linear profile. After subcutaneous administration, ancestim has an absorption half-life of 35-41 hours following a mean lag of 2 hours. When a dose of 5-25 mcg/kg is administered, the peak concentration of 3.6-13.7 ng/ml is reached after 15-24 hours. In preclinical studies, the bioavailability of ancestim was reported to be greater than 60%. After multiple dosing, the steady state was reached after 4-5 days from the beginning of the treatment.
Half Life
In clinical trials, the reported half life for ancestim was between 2-5 hours.
Clearance
The apparent clearance reported for ancestim is approximately 35-40 ml/h/kg.
Elimination Route
In preclinical studies, it was shown that 90% of the administered dose is excreted in the urine.
Innovators Monograph
You find simplified version here Ancestim
