DT-Web

DB00019 - Pegfilgrastim


Identification
Name Pegfilgrastim
Accession Number DB00019 (BIOD00094, BTD00094)
Type biotech
Description PEGylated (at N terminus) form of human G-CSF (Granulocyte colony stimulating factor), 175 residues, produced from E. coli via bacterial fermentation.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 18802.8000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Increases leukocyte production, for treatment in non-myeloid cancer, neutropenia and bone marrow transplant
Mechanism of action Pegfilgrastim 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
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Filgrastim 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.
Toxicity Not Available
Affected organisms Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Granulocyte colony-stimulating factor receptor
Name Granulocyte colony-stimulating factor receptor
Gene Name CSF3R
Pharmacological action yes
Actions agonist
References
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 1.409
Leukocyte elastase
Name Leukocyte elastase
Gene Name ELANE
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 1.9087

Predictions


Id Partner name Gene Name Score
6260 Chymotrypsin-like elastase family member 1 CELA1 0.2672
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