Filgrastim

Identification

Name
Filgrastim
Accession Number
DB00099
Description

Chemotherapy-induced neutropenia (CIN) is a common and serious complication of myelosuppressive chemotherapy. It is associated with significant morbidity and mortality and can increase the cost of cancer therapy. In these cases, colony stimulating factor is necessary to restore important cells for immune function 3.

For over twenty years, granulocyte colony-stimulating factors (G-CSFs; filgrastims) have been a pillar of treatment and prevention of CIN, and have been found to reduce the risk of neutropenia across various patient settings, decrease the incidence of febrile neutropenia, reduce the incidence of infection, reduce the requirement for treatment with antibiotics, and accelerate neutrophil recovery 3.

Filgrastim is a recombinant, non-pegylated human granulocyte colony stimulating factor (G-CSF) analog. It is marketed as the brand name Neupogen by Amgen (initially approved in 1998) and as Nivestym, a biosimilar agent by Pfizer. Nivestym was approved by the FDA on July 20th, 2018 5. Between 1998 and the present, Neupogen/filgrastim has been approved for various indications 8.

Tbo-filgrastim, which is marketed by Sicor Biotech and FDA approved on August 29, 2012, contains the same active ingredient as Neupogen and is biologically similar, but it is formulated to be short-acting 10. On March 6, 2015, the FDA approved the biosimilar Zarxio (filgrastim-sndz) and is indicated for use in the same conditions as Neupogen. Zarxio is marketed by Sandoz 7.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Haematopoietic growth factors
Protein Structure
Db00099
Protein Chemical Formula
C845H1343N223O243S9
Protein Average Weight
18800.0 Da
Sequences
>Amino acid sequence for filgrastim
MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWA
PLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQ
QMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Download FASTA Format
Synonyms
  • Filgrastim-aafi
  • Filgrastim-sndz
  • G-CSF
  • Granulocyte Colony Stimulating Factor
  • Tbo-filgrastim

Pharmacology

Indication

This drug is a leucocyte growth factor Label indicated to:

Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever Label.

Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment in patients with acute myeloid leukemia (AML) Label

Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT) Label

Mobilize autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis Label

Reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia Label.

Neupogen is approved for treatment of patients with radiation-induced myelosuppression following a radiological/nuclear incident 6.

Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Filgrastim binds to the G-CSF receptor and stimulates the production of neutrophils in the bone marrow Label. Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors, in turn, stimulating proliferation and differentiation 9.

G-CSF and its receptor are necessary for basal and stress-induced granulopoiesis, which forms neutrophils. Mice deficient in G-CSF or G-CSFR have severe neutropenia and reduced levels (~50%) of late-stage neutrophil precursors in the bone marrow under normal, resting conditions 4.

Endogenous G-CSF is a lineage-specific colony-stimulating factor that is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and enhances neutrophil progenitor proliferation‚ differentiation, and selected end-cell functions (including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and enhanced expression of certain cell surface antigens). G-CSF is not species-specific and has demonstrated to have negligible direct in vivo or in vitro effects on the production or action of hematopoietic cell types other than the neutrophil and its lineage9.

Mechanism of action

As a G-CSF analog, this drug controls the proliferation of committed progenitor cells and influences their maturation into mature neutrophils. Filgrastim also stimulates the release of neutrophils from bone marrow storage pools and decreases their time to maturation. Filgrastim acts to increase the phagocytic activity of mature neutrophils, thus allowing them to prevent infection. In patients receiving cytotoxic chemotherapy, filgrastim may accelerate neutrophil recovery, leading to a reduction in the duration of the neutropenic phase post chemotherapy Label.

Used in the treatment of chemotherapy-induced neutropenia by enhancing the production of neutrophils, filgrastim acts on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. In one efficacy study, levels of neutrophils returned to baseline by 21 days following completion of chemotherapy and the administration of tbo-filgrastim (fast-acting) 10.

In phase 1 studies involving 96 patients with various non-myeloid malignancies‚ filgrastim administration resulted in a dose-dependent increase in circulating neutrophil counts over the dose range of 1 to 70 mcg/kg/day.

This increase in neutrophil counts was seen whether filgrastim was administered intravenous (1 to 70 mcg/kg twice daily)‚ subcutaneous (1 to 3 mcg/kg once daily)‚ or by continuous subcutaneous (SC) infusion (3 to 11 mcg/kg/day). After the discontinuation of filgrastim therapy‚ neutrophil counts returned to baseline in most cases within only 4 days after Nevistym was used Label.

TargetActionsOrganism
AGranulocyte colony-stimulating factor receptor
stimulator
Humans
UNeutrophil elastase
other/unknown
Humans
Absorption

Absorption and clearance of Neupogen follows first-order pharmacokinetics without concentration dependence. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg of filgrastim resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2-8 hours Label. Filgrastim does not accumulate. It is estimated that when filgrastim is subcutaneously administered, the absolute bioavailability is approximately 62% and 71% for 375 mcg and 750 mcg doses respectively. When 5 mcg/kg tbo-filgrastim is subcutaneously administered, the absolute bioavailability is 33%. It takes 4-6 hours for tho-filgrastim to reach maximum concentration 10.

Volume of distribution

150 mL/kg Label

Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Filgrastim products demonstrate nonlinear pharmacokinetics. The clearance is dependent on filgrastim product concentration in addition to neutrophil count. G-CSF receptor-mediated clearance is saturated by a high concentration of filgrastim products and is diminished by neutropenia. In addition, filgrastim products are cleared by the kidney 9.

Half-life

Elimination half-life was approximately 3.5 hours in both normal subjects and cancer subjects Label

Clearance

0.5 - 0.7 mL/minute/kg after SC administration of 3.45 mcg/kg and 11.5 mcg/kg in both normal subjects and cancer patients Label

Adverse Effects
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Toxicity

There are numerous adverse effects associated with Filgastrim. They are organized by organ system as follows:

Generalized effects

Serious allergic reactions, including anaphylaxis: Permanently discontinue NIVESTYM in patients with serious allergic reactions. With non-myeloid malignancies receiving myelosuppressive anti-cancer drugs (≥ 5% difference in incidence compared to placebo) are pyrexia, pain, rash, cough, and dyspnea Label. With AML (≥ 2% difference in incidence) are pain, epistaxis and rash Label. With severe chronic neutropenia (SCN) (≥ 5% difference in incidence) are pain, anemia, epistaxis, diarrhea, hypoesthesia, and alopecia Label.

Musculoskeletal system

Exacerbation of arthritic symptoms has been uncommonly observed 9.

Spleen

Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture. Cases of splenomegaly and splenic rupture have been reported uncommonly following administration of filgrastim. Some cases of splenic rupture were fatal Label.

Respiratory system

Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS. Discontinue filgrastim in patients with ARDS Label. Pulmonary adverse effects, in particular interstitial lung disease, have been reported after G-CSF administration. Patients with a recent history of lung infiltrates or pneumonia may be at higher risk. The onset of pulmonary signs, such as cough, fever and dyspnea in association with radiological signs of pulmonary infiltrates and deterioration in pulmonary function may be preliminary signs of acute respiratory distress syndrome (ARDS). Filgrastim should be discontinued and appropriate treatment should be given 9.

Hematological system

Fatal sickle cell crises have occurred.

The granulocyte-colony stimulating factor can promote the malignant growth of myeloid cells in vitro and the same effects may be seen on some non-myeloid cells in vitro. The safety and efficacy of filgrastim administration in patients with myelodysplastic syndrome, or chronic myelogenous leukemia have not been established. Filgrastim is not indicated for use in these conditions. Particular care should be taken to distinguish the diagnosis of blast transformation of chronic myeloid leukemia from acute myeloid leukemia 9.

Capillary leak syndrome has been reported after granulocyte colony-stimulating factor administration, and is characterised by hypotension, hypoalbuminaemia, edema and hemoconcentration. Patients who show symptoms of capillary leak syndrome must be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care 9.

Leukocytosis (white blood cell (WBC) > 50 x 109/l) was seen in 41% of donors and transient thrombocytopenia (platelets < 100 x 109/l) following filgrastim and leukapheresis was observed in 35% of donors 9.

Renal system

This drug increases the risk of glomerulonephritis. Evaluate and consider dose-reduction or interruption of filgrastim if causality is likely Label.

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

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
BleomycinThe risk or severity of pulmonary toxicity can be increased when Filgrastim is combined with Bleomycin.
CyclophosphamideThe risk or severity of pulmonary toxicity can be increased when Filgrastim is combined with Cyclophosphamide.
TopotecanThe risk or severity of neutropenia can be increased when Filgrastim is combined with Topotecan.
VinblastineThe risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinblastine.
VincristineThe risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vincristine.
VindesineThe risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vindesine.
VinflunineThe risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinflunine.
VinorelbineThe risk or severity of peripheral neuropathy can be increased when Filgrastim is combined with Vinorelbine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

Products

International/Other Brands
Biocilin / Biofigran / Biofilgran / Endufil / Filatil / Filgen / Gran / Granulokine / Grimatin / Inmunef / Jiexin / Leucogen / Leucostim / Macroleuco / Neukine / Neutromax / Neutroval (Sicor Biotech) / Recombicyte / SciLocyte / Tevagastrim / White-C / Zarzio
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AccofilInjection, solution30000000 [units of filgrastim]/0.5mlIntravenous; SubcutaneousAccord Healthcare Limited2014-09-18Not applicableEU flag
AccofilInjection, solution48000000 [units of filgrastim]/0.5mlIntravenous; SubcutaneousAccord Healthcare Limited2014-09-18Not applicableEU flag
AccofilInjection, solution48000000 [units of filgrastim]/0.5mlIntravenous; SubcutaneousAccord Healthcare Limited2014-09-18Not applicableEU flag
AccofilInjection, solution30000000 [units of filgrastim]/0.5mlIntravenous; SubcutaneousAccord Healthcare Limited2014-09-18Not applicableEU flag
AccofilInjection, solution30000000 [units of filgrastim]/0.5mlIntravenous; SubcutaneousAccord Healthcare Limited2014-09-18Not applicableEU flag
AccofilInjection, solution48000000 [units of filgrastim]/0.5mlIntravenous; SubcutaneousAccord Healthcare Limited2014-09-18Not applicableEU flag
AccofilInjection, solution30000000 [units of filgrastim]/0.5mlIntravenous; SubcutaneousAccord Healthcare Limited2014-09-18Not applicableEU flag
AccofilInjection, solution30000000 [units of filgrastim]/0.5mlIntravenous; SubcutaneousAccord Healthcare Limited2014-09-18Not applicableEU flag
AccofilInjection, solution48000000 [units of filgrastim]/0.5mlIntravenous; SubcutaneousAccord Healthcare Limited2014-09-18Not applicableEU flag
AccofilInjection, solution30000000 [units of filgrastim]/0.5mlIntravenous; SubcutaneousAccord Healthcare Limited2014-09-18Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L03AA02 — Filgrastim
Drug Categories
Chemical TaxonomyProvided by Classyfire
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

Chemical Identifiers

UNII
PVI5M0M1GW
CAS number
121181-53-1

References

Synthesis Reference

Tetsuro Kuga, Hiromasa Miyaji, Moriyuki Sato, Masami Okabe, Makoto Morimoto, Seiga Itoh, Motoo Yamasaki, Yoshiharu Yokoo, Kazuo Yamaguchi, Hajime Yoshida, Yoshinori Komatsu, "Method of producing a polypeptide having human granulocyte colony stimulating factor activity." U.S. Patent US5994518, issued February, 1988.

US5994518
General References
  1. Wang B, Ludden TM, Cheung EN, Schwab GG, Roskos LK: Population pharmacokinetic-pharmacodynamic modeling of filgrastim (r-metHuG-CSF) in healthy volunteers. J Pharmacokinet Pharmacodyn. 2001 Aug;28(4):321-42. [PubMed:11677930]
  2. Krzyzanski W, Wiczling P, Lowe P, Pigeolet E, Fink M, Berghout A, Balser S: Population modeling of filgrastim PK-PD in healthy adults following intravenous and subcutaneous administrations. J Clin Pharmacol. 2010 Sep;50(9 Suppl):101S-112S. doi: 10.1177/0091270010376966. [PubMed:20881223]
  3. Kamioner D, Fruehauf S, Maloisel F, Cals L, Lepretre S, Berthou C: Study design: two long-term observational studies of the biosimilar filgrastim Nivestim (Hospira filgrastim) in the treatment and prevention of chemotherapy-induced neutropenia. BMC Cancer. 2013 Nov 16;13:547. doi: 10.1186/1471-2407-13-547. [PubMed:24237790]
  4. Panopoulos AD, Watowich SS: Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and 'emergency' hematopoiesis. Cytokine. 2008 Jun;42(3):277-88. doi: 10.1016/j.cyto.2008.03.002. Epub 2008 Apr 8. [PubMed:18400509]
  5. FDA Approves Second Neupogen Biosimilar, Nivestym [Link]
  6. FDA Approves Radiation Medical Countermeasure [Link]
  7. Zarxio [Link]
  8. Drugs Approved by the FDA document [Link]
  9. EMA label [File]
  10. TBO filgrastim [File]
UniProt
P09919
Genbank
X03438
KEGG Drug
D03235
PubChem Substance
46505833
RxNav
1433764
ChEMBL
CHEMBL1201567
Therapeutic Targets Database
DAP000113
PharmGKB
PA449626
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Filgrastim
AHFS Codes
  • 20:16.00 — Hematopoietic Agents
FDA label
Download (2.27 MB)
MSDS
Download (125 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedDiagnosticDiabetes Mellitus1
4CompletedPreventionBreast Cancer1
4CompletedPreventionMycoses1
4CompletedSupportive CareBreast Cancer1
4CompletedTreatmentAcute Myeloblastic Leukemia / Myelodysplastic Syndrome1
4CompletedTreatmentAdult Acute Lymphocytic Leukemia2
4CompletedTreatmentAnemia / Graft Versus Host Disease (GVHD) / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes (MDS)1
4CompletedTreatmentAsherman's Syndrome / Endometrium; Atrophy, Cervix1
4CompletedTreatmentBurkitt's Lymphoma / Large Cell Anaplastic Lymphoma / Lymphoma, Lymphoblastic / Mediastinal Neoplasms1
4CompletedTreatmentEarly Breast Cancer2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Amgen Inc.
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous; Subcutaneous30000000 [units of filgrastim]/0.5ml
Injection, solutionIntravenous; Subcutaneous48000000 [units of filgrastim]/0.5ml
InjectionParenteral30 MIO.E./0.5ML
InjectionParenteral0.5 ML
InjectionParenteral30 MIO E/0.5ML
InjectionParenteral48 MIO.E./0.5ML
InjectionParenteral48 MIO E/0.5ML
SolutionIntravenous; Subcutaneous300 mcg
SolutionIntravenous; Subcutaneous480 mcg
Injection, solutionIntravenous; Subcutaneous30 MIU
Injection, solutionIntravenous; Subcutaneous48 MIU
Injection, solution480 mcg/1.6mL
InjectionParenteral0.3 mg
InjectionParenteral0.48 mg
InjectionIntravenous30 miu/0.5ml
Injection, solution300 mcg/0.5mL
Injection, solutionSubcutaneous300 ug/1mL
Injection, solutionSubcutaneous480 ug/1.6mL
Injection, solution, concentrateIntravenous; Subcutaneous30 MU/ml
Injection, solution, concentrateSubcutaneous300 mcg
Injection, solution, concentrateSubcutaneous480 mcg
Injection, solutionSubcutaneous48 MU/0.5ml
SolutionIntravenous; Subcutaneous
Injection, solution300 mcg/1.2mL
Injection, solution75 mcg/0.3mL
Injection
InjectionIntravenous; Subcutaneous15 miu
InjectionIntravenous; Subcutaneous30 miu
InjectionIntravenous; Subcutaneous30 miu/ml
Injection, solution480 mcg/0.5mL
Injection, solutionIntravenous300 ug/1mL
Injection, solutionIntravenous300 ug/0.5mL
Injection, solutionIntravenous480 ug/0.8mL
SolutionIntravenous; Subcutaneous600 mcg
InjectionParenteral300 µg/0.5ml
InjectionParenteral
Injection, solutionIntravenous; Subcutaneous300 mcg/0.5ml
InjectionParenteral480 µg/0.5ml
InjectionParenteral480 UG
Injection, solutionIntravenous; Subcutaneous480 mcg/0.5ml
InjectionParenteral480 UG/0.5ML
Injection; solutionIntravenous; Subcutaneous30 miu/0.5ml
Injection; solutionIntravenous; Subcutaneous48 miu/0.5ml
SolutionIntravenous; Subcutaneous30 millions of units
Injection, solution300 mcg/1mL
Injection, solutionIntravenous; Subcutaneous12 MU/0.2ml
Injection, solutionIntravenous; Subcutaneous12000000 [units of filgrastim]/0.2mL
Injection, solutionIntravenous; Subcutaneous30 MU/0.5ml
Injection, solutionIntravenous; Subcutaneous48 MU/0.5ml
InjectionParenteral12 MIO E/0.2ML
Injection, solutionIntravenous30 MU/0.5ml
InjectionParenteral05 ML
Injection, solutionIntravenous48 MU/0.5ml
Solution
Injection, solutionIntravenous; Subcutaneous300 ug/1mL
Injection, solutionIntravenous; Subcutaneous480 ug/1.6mL
Injection, solutionSubcutaneous300 ug/0.5mL
Injection, solutionSubcutaneous480 ug/0.8mL
SolutionIntravenous; Subcutaneous300 cg
InjectionParenteral30 M UI/0.5 ml
InjectionParenteral48 M UI/0.8 ml
InjectionParenteral0.8 ML
Injection, solutionIntravenous; Subcutaneous30 MUI/0.5ml
Injection, solutionIntravenous; Subcutaneous48 MUI/0.8ml
Injection, solutionIntravenous; Subcutaneous30 MIU/0.5mL
Injection, solutionIntravenous; Subcutaneous48 MIU/0.8mL
Injection, solutionIntravenous; Subcutaneous300 ug/0.5mL
Injection, solutionIntravenous; Subcutaneous480 ug/0.8mL
InjectionParenteral30 MIO E./0.5ML
InjectionParenteral48 MIO E./0.5ML
SolutionIntravenous; Subcutaneous30 million IU
Prices
Unit descriptionCostUnit
Neupogen 480 mcg/0.8ml Solution 1 Box Contains Ten 0.8ml Syringes4998.24USD box
Neupogen 480 mcg/1.6ml Solution 1 Box Contains Ten 1.6ml Syringes4554.58USD box
Neupogen 300 mcg/0.5ml Solution 1 Box Contains Ten 0.5ml Syringes3138.1USD box
Neupogen 480 mcg/1.6 ml vial437.94USD ml
Neupogen 300 mcg/ml vial286.04USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA1341537No2007-07-312024-07-31Canada flag
CA1339071No1997-07-292014-07-29Canada flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)4MSDS
boiling point (°C)100MSDS
hydrophobicity0.209Not Available
isoelectric point5.65Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Stimulator
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 neutroph...
Gene Name
CSF3R
Uniprot ID
Q99062
Uniprot Name
Granulocyte colony-stimulating factor receptor
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. Link DC, Kunter G, Kasai Y, Zhao Y, Miner T, McLellan MD, Ries RE, Kapur D, Nagarajan R, Dale DC, Bolyard AA, Boxer LA, Welte K, Zeidler C, Donadieu J, Bellanne-Chantelot C, Vardiman JW, Caligiuri MA, Bloomfield CD, DiPersio JF, Tomasson MH, Graubert TA, Westervelt P, Watson M, Shannon W, Baty J, Mardis ER, Wilson RK, Ley TJ: Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia. Blood. 2007 Sep 1;110(5):1648-55. Epub 2007 May 9. [PubMed:17494858]
  3. 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]
  4. 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]
  5. 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]
  6. EMA label [File]
  7. TBO filgrastim [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other/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
Uniprot Name
Neutrophil elastase
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. Donini M, Fontana S, Savoldi G, Vermi W, Tassone L, Gentili F, Zenaro E, Ferrari D, Notarangelo LD, Porta F, Facchetti F, Notarangelo LD, Dusi S, Badolato R: G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms. Blood. 2007 Jun 1;109(11):4716-23. Epub 2007 Feb 20. [PubMed:17311988]
  4. 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]
  5. 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]
  6. El Ouriaghli F, Fujiwara H, Melenhorst JJ, Sconocchia G, Hensel N, Barrett AJ: Neutrophil elastase enzymatically antagonizes the in vitro action of G-CSF: implications for the regulation of granulopoiesis. Blood. 2003 Mar 1;101(5):1752-8. Epub 2002 Oct 17. [PubMed:12393522]

Drug created on June 13, 2005 07:24 / Updated on October 25, 2020 09:16

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