Identification

Summary

Filgrastim is a form of recombinant human granulocyte colony stimulating factor used to induce the production of granulocytes and lower infection risk after myelosuppressive therapy.

Brand Names
Accofil, Granix, Grastofil, Neupogen, Nivestim, Nivestym, Ratiograstim, Releuko, Zarxio
Generic Name
Filgrastim
DrugBank Accession Number
DB00099
Background

Filgrastim is a short-acting recombinant, non-pegylated human granulocyte colony-stimulating factor (G-CSF) analog produced by recombinant DNA technology. It has an amino acid sequence identical to endogenous G-CSF, but it is non-glycosylated unlike the endogenous G-CSF and has an N-terminal methionine added in the sequence for expression in E. Coli.8 Human G-CSF is a glycoprotein that regulates the production and release of neutrophils from the bone marrow. Filgrastim mimics the biological actions of G-CSF to increase the levels of neutrophils in the blood.10 It has a number of therapeutic uses, including the management and prevention of infections and febrile neutropenia in patients receiving myelosuppressive chemotherapy or radiation therapy. It is also used to manage severe chronic neutropenia and mobilize hematopoietic progenitor cells to the peripheral blood for collection by leukapheresis in patients undergoing peripheral blood progenitor cell collection and therapy.8

Filgrastim was approved in the US in 1991 and there are biosimilars available with similar therapeutic indications.3 Tbo-filgrastim was approved by the FDA on August 29, 2012.9 Filgrastim-sndz was approved on March 6, 2015 12 and filgrastim-ayow was approved on March 2, 2022.13 A long-acting, pegylated G-CSF, pegfilgrastim, was made available to increase the duration of action of the drug.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Haematopoietic growth factors
Protein Structure
Protein Chemical Formula
C845H1339N223O243S9
Protein Average Weight
18800.0 Da (approximate)
Sequences
>Protein sequence
MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWA
PLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQ
QMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
References:
  1. KEGG DRUG: Filgrastim [Link]
Download FASTA Format
Synonyms
  • Filgrastim
  • Filgrastim-aafi
  • Filgrastim-sndz
  • G-CSF
  • Granulocyte Colony Stimulating Factor
  • Tbo-filgrastim

Pharmacology

Indication

Filgrastim is 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.8

Filgrastim is indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia.8

Filgrastim is indicated to 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.8

Filgrastim is indicated for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.8

Filgrastim is indicated for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia.8

Filgrastim is indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation.8

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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Filgrastim is used to reduce the incidence, severity and duration of neutropenia and febrile neutropenia in patients undergoing cytotoxic chemotherapy. In clinical trials in patients, filgrastim reduced the duration of febrile neutropenia, antibiotic use, and hospitalization after induction chemotherapy for acute myelogenous leukemia or myeloablative therapy followed by bone marrow transplantation; however, the incidence of fever and documented infections were not reduced in either setting.10

Filgrastim is also used to mobilize hematopoietic progenitor cells into the peripheral blood in order to reduce the risk for bleeding complications and the need for platelet transfusions. Recipients of allogeneic PBPCs mobilized with filgrastim experienced significantly more rapid hematological recovery, leading to a significant decrease in time to unsupported platelet recovery when compared with allogeneic bone marrow transplantation.10

Filgrastim causes a dose-dependent increase in circulating neutrophil counts within 24 hours of administration. Filgrastim can also cause a minor increase in monocyte and lymphocyte counts, but the clinical significance of these effects is unknown.8 In some patients, filgrastim also caused a minor increase in the number of circulating eosinophils and basophils relative to baseline; however, these patients may already have had elevated eosinophils and basophils prior to filgrastim treatment. Following termination of filgrastim therapy, circulating neutrophil counts decrease by 50% within one to two days, and to normal levels within one to seven days. As with other hematopoietic growth factors, G-CSF has shown in vitro stimulating properties on human endothelial cells.10

Mechanism of action

Neutrophils are critical granulocytes involved in the acute inflammatory response and host defences against bacterial infections.5 They also contribute to long-term adaptive immunity by promoting immediate host immune response and attracting other cells, such as macrophages and dendritic cells. As neutrophils promote both the initiation and the maintenance of inflammation at sites of infection, suppressed neutrophil responses lead to extreme susceptibility to infection.2 Low neutrophil levels, or neutropenia, caused by chronic neutropenia, myelosuppressive chemotherapy, and radiation therapy increases the risk of infection and related events.4 Neutropenia caused by chemotherapy or radiation therapy can further progress into febrile neutropenia, which is associated with an elevated risk for life-threatening systemic infections and chemotherapy-associated morbidity and mortality.1

The production and release of functional neutrophils from the bone marrow are normally regulated by granulocyte colony-stimulating factors (G-CSF), which are major cytokine regulators of neutrophilic granulocytes.2 G-CSFs act on hematopoietic cells by binding to specific cell surface receptors to stimulate the proliferation‚ differentiation‚ and maturation of neutrophil progenitors. G-CSF also induces some end-cell functional activation of neutrophils, including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and the increased expression of some cell surface antigens.8 Filgrastim is a short-acting recombinant G-CSF that mimics the biological actions of endogenous G-CSF. It also facilitates the release of neutrophils from the bone marrow into the blood to reduce the incidence of infection and manage neutropenia.3,4

TargetActionsOrganism
AGranulocyte colony-stimulating factor receptor
stimulator
Humans
Absorption

Filgrastim exhibits nonlinear pharmacokinetics. 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 to 8 hours.

Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70%.8

Volume of distribution

After intravenous administration, the volume of distribution averaged 150 mL/kg.8 There is no evidence of drug accumulation.10

Protein binding

There is limited information available.

Metabolism

Like other G-CSF compounds, filgrastim is cleared from plasma via neutrophil-mediated clearance involving internalization via G-CSF receptors and degradation within the neutrophil. Filgrastim is also subject to extracellular proteolytic degradation by neutrophil elastase: this enzyme rapidly cleaves filgrastim and renders it inactive.6,7

Route of elimination

There is limited information available; however, filgrastim is subject to renal elimination.7

Half-life

After intravenous administration, the elimination half-life of filgrastim was approximately 3.5 hours in both normal subjects and patients with cancer. Single parenteral doses or daily intravenous doses‚ over a 14-day period‚ resulted in comparable half-lives. The half-lives were similar for intravenous administration (231 minutes‚ following doses of 34.5 mcg/kg) and for subcutaneous administration (210 minutes‚ following filgrastim dosages of 3.45 mcg/kg).8

Clearance

Clearance rates of filgrastim were approximately 0.5 to 0.7 mL/minute/kg after intravenous administration.8

Adverse Effects
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Toxicity

The oral LD50 in mouse and rat was >3 mg/kg. The intravenous LD50 in rat was also >3 mg/kg.11

There is limited information regarding filgrastim overdose. The maximum tolerated dose of filgrastim has not been determined. In clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ white blood cell counts greater than 100,000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the bone marrow transplantation studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day.8

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.
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Food Interactions
No interactions found.

Products

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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, solution70000000 U/0.73mlIntravenous; SubcutaneousAccord Healthcare S.L.U.2022-06-09Not applicableEU flag
AccofilInjection, solution12000000 U/0.2mlIntravenous; SubcutaneousAccord Healthcare S.L.U.2022-06-08Not applicableEU flag
AccofilInjection, solution48000000 U/0.5mlIntravenous; SubcutaneousAccord Healthcare S.L.U.2016-09-07Not applicableEU flag
AccofilInjection, solution48000000 U/0.5mlIntravenous; SubcutaneousAccord Healthcare S.L.U.2016-09-07Not applicableEU flag
AccofilInjection, solution48000000 U/0.5mlIntravenous; SubcutaneousAccord Healthcare S.L.U.2016-09-07Not applicableEU flag
AccofilInjection, solution30000000 U/0.5mlIntravenous; SubcutaneousAccord Healthcare S.L.U.2016-09-07Not applicableEU flag
AccofilInjection, solution12000000 U/0.2mlIntravenous; SubcutaneousAccord Healthcare S.L.U.2022-06-08Not applicableEU flag
AccofilInjection, solution70000000 U/0.73mlIntravenous; SubcutaneousAccord Healthcare S.L.U.2022-06-09Not applicableEU flag
AccofilInjection, solution30000000 U/0.5mlIntravenous; SubcutaneousAccord Healthcare S.L.U.2016-09-07Not applicableEU flag
AccofilInjection, solution12000000 U/0.2mlIntravenous; SubcutaneousAccord Healthcare S.L.U.2022-06-08Not applicableEU flag

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
Affected organisms
  • Humans and other mammals

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. 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. [Article]
  2. 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. [Article]
  3. Aghedo BO, Gupta V: Filgrastim . [Article]
  4. Dale DC, Crawford J, Klippel Z, Reiner M, Osslund T, Fan E, Morrow PK, Allcott K, Lyman GH: A systematic literature review of the efficacy, effectiveness, and safety of filgrastim. Support Care Cancer. 2018 Jan;26(1):7-20. doi: 10.1007/s00520-017-3854-x. Epub 2017 Sep 22. [Article]
  5. Boxer L, Dale DC: Neutropenia: causes and consequences. Semin Hematol. 2002 Apr;39(2):75-81. doi: 10.1053/shem.2002.31911. [Article]
  6. Abdolzade-Bavil A, von Kerczek A, Cooksey BA, Kaufman T, Krasney PA, Pukac L, Gorlach M, Lammerich A, Scheckermann C, Allgaier H, Shen WD, Liu PM: Differential sensitivity of lipegfilgrastim and pegfilgrastim to neutrophil elastase correlates with differences in clinical pharmacokinetic profile. J Clin Pharmacol. 2016 Feb;56(2):186-94. doi: 10.1002/jcph.578. Epub 2015 Sep 1. [Article]
  7. Scholz M, Ackermann M, Engel C, Emmrich F, Loeffler M, Kamprad M: A pharmacokinetic model of filgrastim and pegfilgrastim application in normal mice and those with cyclophosphamide-induced granulocytopaenia. Cell Prolif. 2009 Dec;42(6):813-22. doi: 10.1111/j.1365-2184.2009.00638.x. Epub 2009 Aug 17. [Article]
  8. DailyMed Label: NEUPOGEN (filgrastim) injection, for subcutaneous or intravenous use [Link]
  9. DailyMed Label; GRANIX (tbo-filgrastim) injection, for subcutaneous use [Link]
  10. EMA Summary of Product Characteristics: HEXAL (filgrastim) subcutaneous or intravenous injection [Link]
  11. Hospira Safety Data Sheet: NIVESTYM (Filgrastim-aafi) [Link]
  12. Drugs@FDA: Zarxio (filgrastim-sndz) [Link]
  13. Business Wire News: Kashiv Biosciences Receives Approval for Its First Biosimilar RELEUKOTM (filgrastim-ayow) [Link]
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

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedDiagnosticDiabetes Mellitus1
4CompletedPreventionBreast Cancer1
4CompletedPreventionMycoses1
4CompletedSupportive CareBreast Cancer1
4CompletedTreatmentAnaplastic Large Cell Lymphoma / Burkitt Lymphoma (BL) / Lymphoma, Lymphoblastic / Mediastinal Neoplasms1
4CompletedTreatmentAnemia / Graft Versus Host Disease (cGvHD) / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes (MDS)1
4CompletedTreatmentAsherman's Syndrome / Endometrium; Atrophy, Cervix1
4CompletedTreatmentEarly Breast Cancer2
4CompletedTreatmentLeukemia, Lymphocytic, Acute, Adult2
4CompletedTreatmentLeukemia, Myeloblastic, Acute / Myelodysplastic Syndromes (MDS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Amgen Inc.
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous; Subcutaneous12000000 U/0.2ml
Injection, solutionIntravenous; Subcutaneous30000000 U/0.5ml
Injection, solutionIntravenous; Subcutaneous48000000 U/0.5ml
Injection, solutionIntravenous; Subcutaneous70000000 U/0.73ml
InjectionParenteral30 MIO.E./0.5ML
InjectionParenteral0.5 ML
Injection, solutionIntravenous; Subcutaneous300 mcg/0.5mL
InjectionParenteral30 MIO E/0.5ML
InjectionParenteral48 MIO.E./0.5ML
Injection, solutionIntravenous; Subcutaneous480 mcg/0.5mL
InjectionParenteral48 MIO E/0.5ML
SolutionIntravenous; Subcutaneous480 mcg
Injection, solutionIntravenous; Subcutaneous30 MIU
Injection, solutionIntravenous; Subcutaneous48 MIU
SolutionIntravenous; Subcutaneous300 mcg
Injection, solutionIntravenous; Subcutaneous60 MU/ml
Injection, solutionIntravenous; Subcutaneous96 MU/ml
InjectionParenteral0.3 mg
InjectionParenteral0.48 mg
InjectionIntravenous
Solution300 mcg/1ml
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; Subcutaneous300 mcg / 0.5 mL
SolutionIntravenous; Subcutaneous480 mcg / 0.8 mL
SolutionSubcutaneous300 mcg
SolutionSubcutaneous480 mcg
Injection
InjectionIntravenous; Subcutaneous
Injection, solution480 mcg/ml
Injection, solution
Injection, solutionIntravenous300 ug/0.5mL
Injection, solutionIntravenous300 ug/1mL
Injection, solutionIntravenous480 ug/0.8mL
SolutionIntravenous; Subcutaneous300 mcg / mL
SolutionIntravenous; Subcutaneous600 mcg / mL
InjectionParenteral300 µg/0.5ml
InjectionParenteral30 MIO.E.
InjectionParenteral300 UG/1ML
InjectionParenteral480 µg/0.5ml
InjectionParenteral48 MIO.E.
InjectionParenteral480 UG
InjectionParenteral480 UG/0.5ML
InjectionIntravenous; Subcutaneous300 mcg/ml
InjectionIntravenous; Subcutaneous480 mcg/1.6ml
InjectionIntravenous; Subcutaneous30 mu/0.5ml
InjectionIntravenous; Subcutaneous48 mu/0.5ml
Injection; solutionIntravenous; Subcutaneous
SolutionIntravenous; Subcutaneous30 millions of units
Injection, solution480 mcg/1vial
Injection, solutionIntravenous; Subcutaneous12 MU/0.2ml
Injection, solutionIntravenous; Subcutaneous12000000 [units of filgrastim]/0.2mL
Injection, solutionIntravenous; Subcutaneous30 MU/0.5ml
Injection, solutionIntravenous; Subcutaneous30000000 [units of filgrastim]/0.5mL
Injection, solutionIntravenous; Subcutaneous48 MU/0.5ml
Injection, solutionIntravenous; Subcutaneous48000000 [units of filgrastim]/0.5mL
InjectionParenteral12 MIO E/0.2ML
InjectionParenteral0.2 ML
Injection, solutionIntravenous; Subcutaneous
Injection, solutionIntravenous drip; Subcutaneous0.120 mg/0.2ml
Injection, solutionIntravenous
SolutionIntravenous drip; Subcutaneous0.300 mg/0.5ml
InjectionParenteral05 ML
SolutionIntravenous drip; Subcutaneous0.480 mg/0.5ml
Injection, solution120 mcg/0.2ml
Injection, solutionIntravenous; Subcutaneous300 ug/1mL
Injection, solutionIntravenous; Subcutaneous480 ug/1.6mL
Injection, solutionSubcutaneous300 ug/0.5mL
Injection, solutionSubcutaneous480 ug/0.8mL
SolutionIntravenous; Subcutaneous480 mcg / 1.6 mL
SolutionIntravenous; Subcutaneous300 cg
Injection, solutionIntravenous; Subcutaneous30 MIU/0.5ml
Injection, solutionIntravenous; Subcutaneous48 MIU/0.8ml
InjectionParenteral30 M UI/0.5 ml
InjectionParenteral48 M UI/0.8 ml
InjectionParenteral0.8 ML
Injection, solutionIntravenous; Subcutaneous30 MUI/0.5ml
Injection, solutionIntravenous; Subcutaneous300 µg/0.5 ml
Injection, solutionIntravenous; Subcutaneous48 MUI/0.8ml
Injection, solutionIntravenous; Subcutaneous480 µg/0.8 ml
Injection, solutionIntravenous; Subcutaneous300 ug/0.5mL
Injection, solutionIntravenous; Subcutaneous480 ug/0.8mL
Injection, solutionIntravenous; Subcutaneous30 MU
Injection, solutionIntravenous; Subcutaneous48 MU
Injection, solution480 mcg/1ml
InjectionParenteral30 MIO E./0.5ML
SolutionIntravenous; Subcutaneous300 mcg/0.5ml
InjectionParenteral48 MIO E./0.5ML
SolutionIntravenous; Subcutaneous480 mcg/0.5ml
Injection, solutionIntravenous; Subcutaneous0.3 mg/0.5ml
SolutionIntravenous; Subcutaneous30 million IU
Injection, solution10000 iu/10ml
Injection, solution300 mcg/0.5ml
Injection, solution480 mcg/0.5ml
Solution300 mcg/1vial
Solution480 mcg/1vial
Injection, solution300 mcg/ml
Injection, solution300 mcg/1ml
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

Properties

State
Liquid
Experimental Properties
PropertyValueSource
boiling point (°C)100https://www.msds.amgen.com/-/media/Themes/Amgen/msds-amgen-com/msds-amgen-com/documents/neupogen_safety_data_sheet_20130218_rev_3.pdf
isoelectric point5.65Not Available

Targets

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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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. EMA label [File]
  7. TBO filgrastim [File]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Abdolzade-Bavil A, von Kerczek A, Cooksey BA, Kaufman T, Krasney PA, Pukac L, Gorlach M, Lammerich A, Scheckermann C, Allgaier H, Shen WD, Liu PM: Differential sensitivity of lipegfilgrastim and pegfilgrastim to neutrophil elastase correlates with differences in clinical pharmacokinetic profile. J Clin Pharmacol. 2016 Feb;56(2):186-94. doi: 10.1002/jcph.578. Epub 2015 Sep 1. [Article]
  2. Scholz M, Ackermann M, Engel C, Emmrich F, Loeffler M, Kamprad M: A pharmacokinetic model of filgrastim and pegfilgrastim application in normal mice and those with cyclophosphamide-induced granulocytopaenia. Cell Prolif. 2009 Dec;42(6):813-22. doi: 10.1111/j.1365-2184.2009.00638.x. Epub 2009 Aug 17. [Article]

Drug created at June 13, 2005 13:24 / Updated at June 03, 2022 07:24