Identification

Name
Ancestim
Accession Number
DB09103
Type
Biotech
Groups
Approved, Investigational, Withdrawn
Biologic Classification
Protein Based Therapies
Haematopoietic growth factors
Description

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.[5] Ancestim was developed by Amgen and sold to Biovitrium, now Swedish Orphan Biovitrum, in December 2008. It was submitted to the FDA under the status of recommendation for approval with a 10 to 1 votes.[2] It was also approved by Health Canada in 1999 but it is currently under the status of canceled post-market.[4]

Protein structure
Db09103
Protein chemical formula
C1662H2650N422O512S18
Protein average weight
18540.0 Da (non-glycosylated)
Sequences
>>Sequence Stem Cell Factor<<<<
MEGICRNRVTNNVKDVTKLVANLPKDYMITLKYVPGMDVLPSHCWISEMVVQLSDSLTDL
LDKFSNISEGLSNYSIIDKLVNIVDDLVECVKENSSKDLKKSFKSPEPRLFTPEEFFRIF
NRSIDAFKDFVVASETSDCVVSSTLSPEKDSRVSVTKPFMLPPVA
Download FASTA Format
Synonyms
Not Available
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
StemgenAncestim (1875 mcg) + Water (5 ml)Kit; Powder, for solutionSubcutaneousBiovitrum Ab (Publ)1999-09-202012-12-31Canada
StemgenAncestim (2500 mcg) + Water (5 ml)Kit; Powder, for solutionSubcutaneousBiovitrum Ab (Publ)Not applicableNot applicableCanada
Categories
UNII
PYB4Q6JG41
CAS number
163545-26-4

Pharmacology

Indication

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.[7] 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.[6]

Pharmacodynamics

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.[6]

Mechanism of action

Ancestim alone is unable to increase peripheral blood progenitor cells so it has to be administered with filgastrim, a granulocyte colony-stimulating factor.[3] 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.[1]

TargetActionsOrganism
AMast/stem cell growth factor receptor Kit
agonist
Human
Absorption

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.[6]

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.[6]

Protein binding
Not Available
Metabolism

Administration of ancestim in preclinical trials have proven that from the excreted dose all of it is formed by degraded ancestim into lower molecular weigth products.[6]

Route of elimination

In preclinical studies, it was shown that 90% of the administered dose is excreted in the urine.[6]

Half life

In clinical trials, the reported half life for ancestim was between 2-5 hours.[6]

Clearance

The apparent clearance reported for ancestim is approximately 35-40 ml/h/kg.[6]

Toxicity

Ancestim was not genotoxic for gene mutation or chromosomal damage and it did not have any effect in fertility.[6]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Ronnstrand L: Signal transduction via the stem cell factor receptor/c-Kit. Cell Mol Life Sci. 2004 Oct;61(19-20):2535-48. doi: 10.1007/s00018-004-4189-6. [PubMed:15526160]
  2. Trahan P. (1999). Clinical Handbook for biotherapy. Jones and Bartlett Publishers Inc..
  3. Galbraith A., Bullock S., Manias E., Hunt B., and Richards A. (2013). Fundamentals of Pharmacology: An applied approach for nursing and health (2nd ed.). Pearson Education Limited. [ISBN:1741031443]
  4. Health Canada [Link]
  5. Sobi [Link]
  6. Stemgen monograph [Link]
  7. Stemgen monograph [Link]
External Links
PubChem Substance
347910405
Wikipedia
Ancestim
ATC Codes
L03AA12 — Ancestim
MSDS
Download (133 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Unknown StatusTreatmentMyelodysplasia1
2CompletedTreatmentMultiple Myeloma (MM)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit; powder, for solutionSubcutaneous
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)230ºC'MSDS'
boiling point (°C)520ºC at 760 mmHg'MSDS'
water solubilityInsoluble'MSDS'
isoelectric point5.86'MSDS'

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
References
  1. Ronnstrand L: Signal transduction via the stem cell factor receptor/c-Kit. Cell Mol Life Sci. 2004 Oct;61(19-20):2535-48. doi: 10.1007/s00018-004-4189-6. [PubMed:15526160]
  2. Barnett A. (2012). Type 2 diabetes (2nd ed.). Oxford.
  3. Stemgen monograph [Link]

Drug created on September 16, 2015 16:07 / Updated on June 02, 2018 08:16