You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NamePegfilgrastim
Accession NumberDB00019  (BTD00094, BIOD00094)
TypeBiotech
GroupsApproved
DescriptionPEGylated (at N terminus) form of human G-CSF (Granulocyte colony stimulating factor), 175 residues, produced from E. coli via bacterial fermentation.
Protein structureDb00019
Related Articles
Protein chemical formulaC845H1343N223O243S9
Protein average weight18802.8 Da
Sequences
> Pegfilgrastim sequence
MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWA
PLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQ
QMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Download FASTA Format
Synonyms
G-CSF
Granulocyte colony-stimulating factor precursor
Lenograstim
N-(3-Hydroxypropyl)Methionylcolony-stimulating Factor (human), 1-Ether with .Alpha.-Methyl-.Omega.-Hydroxypoly(Oxyethylene)
Pluripoietin
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Neulastainjection6 mg/.6mLsubcutaneousAmgen Inc2002-04-01Not applicableUs
NeulastakitsubcutaneousAmgen Inc2002-04-01Not applicableUs
Neulastasolution10 mgsubcutaneousAmgen Canada Inc2004-03-12Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NeupopegSolution for injection6 mgSubcutaneous useDompé Biotec S.P.A.2002-08-22Not applicableEu
NeupopegSolution for injection6 mgSubcutaneous useDompé Biotec S.P.A.2002-08-22Not applicableEu
NeupopegSolution for injection6 mgSubcutaneous useDompé Biotec S.P.A.2002-08-22Not applicableEu
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII3A58010674
CAS number208265-92-3
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationIncreases leukocyte production, for treatment in non-myeloid cancer, neutropenia and bone marrow transplant
PharmacodynamicsUsed in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils. Pegfilgrastim acts on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. Pegfilgrastim has reduced renal clearance and prolonged persistence in vivo as compared to Filgrastim.
Mechanism of actionPegfilgrastim binds to the G-CSF receptor. As a G-CSF analog, it controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Pegfilgrastim also stimulates the release of neutrophils from bone marrow storage pools and reduces their maturation time. Pegfilgrastim acts to increase the phagocytic activity of mature neutrophils. In patients receiving cytotoxic chemotherapy, pegfilgrastim can accelerate neutrophil recovery, leading to a reduction in duration of the neutropenic phase
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationFilgrastim is primarily eliminated by the kidney and neutrophils/neutrophil precursors; the latter presumably involves binding of the growth factor to the G-CSF receptor on the cell surface, internalization of the growth factor-receptor complexes via endocytosis, and subsequent degradation inside the cells. Pegylation of filgrastim renders renal clearance insignificant, which was demonstrated in bilaterally nephrectomized rats and confirmed in subjects with renal impairment. As a result, the neutrophil-mediated clearance is the predominant elimination pathway for pegfilgrastim. During chemotherapy-induced neutropenia, the clearance of pegfilgrastim is significantly reduced and the concentration of pegfilgrastim is sustained until onset of neutrophil recovery.
Half life15-80 hrs
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injectionsubcutaneous6 mg/.6mL
Kitsubcutaneous
Solutionsubcutaneous10 mg
Solution for injectionSubcutaneous use6 mg
Prices
Unit descriptionCostUnit
Neulasta 6 mg/0.6 ml syringe4102.37USD syringe
Neulasta 6 mg/0.6ml Solution 0.6ml Syringe4026.05USD syringe
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1339071 No1997-07-292014-07-29Canada
CA1341537 No2007-07-312024-07-31Canada
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point60 °CLuo, P., Protein Science 11:1218-1226 (2002)
hydrophobicity0.209Not Available
isoelectric point5.65Not Available
References
Synthesis ReferenceNot Available
General References
  1. Yang BB, Kido A: Pharmacokinetics and pharmacodynamics of pegfilgrastim. Clin Pharmacokinet. 2011 May;50(5):295-306. doi: 10.2165/11586040-000000000-00000. [PubMed:21456630 ]
External Links
ATC CodesL03AA10L03AA13
AHFS Codes
  • 20:16.00
PDB Entries
FDA labelDownload (50 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
PegloticaseThe therapeutic efficacy of Pegfilgrastim can be decreased when used in combination with Pegloticase.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Receptor activity
Specific Function:
Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differientation and survival of cells along the neutrophilic lineage. In addition it may function in some adhesion or recognition events at the cell surface.
Gene Name:
CSF3R
Uniprot ID:
Q99062
Molecular Weight:
92155.615 Da
References
  1. Erkeland SJ, Aarts LH, Irandoust M, Roovers O, Klomp A, Valkhof M, Gits J, Eyckerman S, Tavernier J, Touw IP: Novel role of WD40 and SOCS box protein-2 in steady-state distribution of granulocyte colony-stimulating factor receptor and G-CSF-controlled proliferation and differentiation signaling. Oncogene. 2007 Mar 29;26(14):1985-94. Epub 2006 Sep 25. [PubMed:17001306 ]
  2. Elsasser A, Franzen M, Kohlmann A, Weisser M, Schnittger S, Schoch C, Reddy VA, Burel S, Zhang DE, Ueffing M, Tenen DG, Hiddemann W, Behre G: The fusion protein AML1-ETO in acute myeloid leukemia with translocation t(8;21) induces c-jun protein expression via the proximal AP-1 site of the c-jun promoter in an indirect, JNK-dependent manner. Oncogene. 2003 Aug 28;22(36):5646-57. [PubMed:12944913 ]
  3. Ward AC: The role of the granulocyte colony-stimulating factor receptor (G-CSF-R) in disease. Front Biosci. 2007 Jan 1;12:608-18. [PubMed:17127322 ]
  4. Zhuang D, Qiu Y, Haque SJ, Dong F: Tyrosine 729 of the G-CSF receptor controls the duration of receptor signaling: involvement of SOCS3 and SOCS1. J Leukoc Biol. 2005 Oct;78(4):1008-15. Epub 2005 Jul 20. [PubMed:16033816 ]
  5. Cao YR, Shao ZH, Liu H, Shi J, Bai J, Tu MF, Wang HQ, Xing LM, Cui ZZ, Sun J, Jia HR, Yang TY: [The response of bone marrow hematopoietic cells to G-CSF in paroxysmal nocturnal hemoglobinuria patients]. Zhonghua Xue Ye Xue Za Zhi. 2005 Apr;26(4):235-8. [PubMed:15949269 ]
  6. Kotto-Kome AC, Fox SE, Lu W, Yang BB, Christensen RD, Calhoun DA: Evidence that the granulocyte colony-stimulating factor (G-CSF) receptor plays a role in the pharmacokinetics of G-CSF and PegG-CSF using a G-CSF-R KO model. Pharmacol Res. 2004 Jul;50(1):55-8. [PubMed:15082029 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serine-type endopeptidase activity
Specific Function:
Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.
Gene Name:
ELANE
Uniprot ID:
P08246
Molecular Weight:
28517.81 Da
References
  1. Carter CR, Whitmore KM, Thorpe R: The significance of carbohydrates on G-CSF: differential sensitivity of G-CSFs to human neutrophil elastase degradation. J Leukoc Biol. 2004 Mar;75(3):515-22. Epub 2003 Dec 4. [PubMed:14657210 ]
  2. Jian MY, Koizumi T, Tsushima K, Fujimoto K, Kubo K: Effects of granulocyte colony-stimulating factor (G-CSF) and neutrophil elastase inhibitor (ONO-5046) on acid-induced lung injury in rats. Inflammation. 2004 Dec;28(6):327-36. [PubMed:16245075 ]
  3. Pelus LM, Bian H, King AG, Fukuda S: Neutrophil-derived MMP-9 mediates synergistic mobilization of hematopoietic stem and progenitor cells by the combination of G-CSF and the chemokines GRObeta/CXCL2 and GRObetaT/CXCL2delta4. Blood. 2004 Jan 1;103(1):110-9. Epub 2003 Sep 4. [PubMed:12958067 ]
  4. Druhan LJ, Ai J, Massullo P, Kindwall-Keller T, Ranalli MA, Avalos BR: Novel mechanism of G-CSF refractoriness in patients with severe congenital neutropenia. Blood. 2005 Jan 15;105(2):584-91. Epub 2004 Sep 7. [PubMed:15353486 ]
  5. Schepers H, Wierenga AT, van Gosliga D, Eggen BJ, Vellenga E, Schuringa JJ: Reintroduction of C/EBPalpha in leukemic CD34+ stem/progenitor cells impairs self-renewal and partially restores myelopoiesis. Blood. 2007 Aug 15;110(4):1317-25. Epub 2007 May 2. [PubMed:17475913 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23