Sargramostim

Identification

Summary

Sargramostim is a modified form of recombinant human granulocyte-macrophage colony stimulating factor used to increase immune cell production after myelosuppressive therapy or bone marrow transplant.

Brand Names
Leukine
Generic Name
Sargramostim
DrugBank Accession Number
DB00020
Background

Sargramostim is a human recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) expressed in yeast. It is a glycoprotein that is 127 residues. Substitution of Leu23 leads to a difference from native protein.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Haematopoietic growth factors
Protein Structure
Db00020
Protein Chemical Formula
C639H1006N168O196S8
Protein Average Weight
14434.5 Da
Sequences
>DB00020 sequence
APARSPSPSTQPWEHVNAIQEALRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE
LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD
CWEPVQE
Download FASTA Format
Synonyms
  • Recombinant human granulocyte-macrophage colony stimulating factor
  • rGM-CSF
  • rHu GM-CSF
  • Sargramostim
External IDs
  • B1 61.012
  • B1-61012

Pharmacology

Indication

For the treatment of cancer and bone marrow transplant

Pharmacology
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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
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Avoid life-threatening adverse drug events & improve clinical decision support.
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Pharmacodynamics

Sargramostim is used in the treatment of bone marrow transplant recipients or those exposed to chemotherapy an recovering from acut myelogenous leukemia, Leukine or GM-CSF is a hematopoietic growth factor which stimulates the survival, clonal expansion (proliferation) and differentiation of hematopoietic progenitor cells. GM-CSF is also capable of activating mature granulocytes and macrophages. After a bone marrow transplant or chemotherapy, patients have a reduced capacity to produce red and white blood cells. Supplementing them with external sources of GM-CSF helps bring the level of neutrophils back to normal so that they can better fight infections.

Mechanism of action

Sargramostim binds to the Granulocyte-macrophage colony stimulating factor receptor (GM-CSF-R-alpha or CSF2R) which stimulates a JAK2 STAT1/STAT3 signal transduction pathway. This leads to the production of hemopoietic cells and neutrophils

TargetActionsOrganism
AGranulocyte-macrophage colony-stimulating factor receptor subunit alpha
agonist
Humans
AInterleukin-3 receptor subunit alpha
agonist
Humans
ACytokine receptor common subunit beta
agonist
Humans
USyndecan-2
agonist
Humans
UBone marrow proteoglycanNot AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance
  • 420 mL/min/m2 [Normal people with liquid LEUKINE (IV)]
  • 431 mL/min/m2 [Normal people with lyophilized LEUKINE (IV)]
  • 549 mL/min/m2 [Normal people with liquid LEUKINE (SC)]
  • 529 mL/min/m2 [Normal people with lyophilized LEUKINE (SC)]
Adverse Effects
Adverseeffects
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Toxicity

Not Available

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 adverse effects can be increased when Sargramostim is combined with Bleomycin.
CyclophosphamideThe risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Sargramostim.
VinblastineThe risk or severity of peripheral neuropathy can be increased when Sargramostim is combined with Vinblastine.
VincristineThe risk or severity of peripheral neuropathy can be increased when Sargramostim is combined with Vincristine.
VindesineThe risk or severity of peripheral neuropathy can be increased when Sargramostim is combined with Vindesine.
VinflunineThe risk or severity of peripheral neuropathy can be increased when Sargramostim is combined with Vinflunine.
VinorelbineThe risk or severity of peripheral neuropathy can be increased when Sargramostim is combined with Vinorelbine.
Interactions
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Food Interactions
No interactions found.

Products

Products2
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International/Other Brands
Leucomax (Novartis)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LeukineLiquid500 ug/1mLSubcutaneousBerlex2007-12-062007-12-06US flag
LeukineInjection, powder, for solution250 ug/1mLSubcutaneousBayer1991-09-052012-09-21US flag
LeukineInjection, powder, for solution250 ug/1mLIntravenous; SubcutaneousGenzyme Corporation2010-03-152016-06-30US flag
LeukineInjection, solution500 ug/1mLIntravenous; SubcutaneousPartner Therapeutics, Inc1991-03-052012-05-08US flag
LeukineInjection, powder, for solution250 ug/1mLIntravenous; SubcutaneousSanofi Aventis1991-05-012021-12-30US flag
LeukineLiquid500 ug/1mLSubcutaneousBayer1991-03-052012-09-21US flag
LeukineLiquid500 ug/1mLIntravenous; SubcutaneousGenzyme Corporation2010-03-152013-12-31US flag
LeukineInjection, powder, lyophilized, for solution250 ug/1mLIntravenous; SubcutaneousPartner Therapeutics, Inc1991-03-05Not applicableUS flag
LeukineLiquid500 ug/1mLIntravenous; SubcutaneousSanofi Aventis1996-12-012021-12-30US flag
LeukineLiquid500 ug/1mLIntravenous; SubcutaneousPhysicians Total Care, Inc.1996-12-012012-06-30US flag

Categories

ATC Codes
L03AA09 — Sargramostim
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
5TAA004E22
CAS number
123774-72-1

References

Synthesis Reference

Kaname Sugimoto, "Process for the production of human colony-stimulating factor." U.S. Patent US4621050, issued May, 1983.

US4621050
General References
Not Available
UniProt
P04141
Genbank
M13207
PubChem Substance
46507000
RxNav
69634
ChEMBL
CHEMBL1201670
Therapeutic Targets Database
DAP001053
PharmGKB
PA164748631
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sargramostim

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentCritical Injury (Trauma) in Children1
4CompletedTreatmentCoronavirus Disease 2019 (COVID‑19)1
4CompletedTreatmentLeukemia, Myeloblastic, Acute1
4CompletedTreatmentMalignant Melanoma of Skin1
4RecruitingTreatmentPediatric Sepsis-induced MODS1
3Active Not RecruitingTreatmentLocalized Resectable Neuroblastoma / Localized Unresectable Neuroblastoma / Recurrent Neuroblastoma / Regional Neuroblastoma / Stage 4 Neuroblastoma / Stage 4S Neuroblastoma1
3CompletedPreventionBreast Cancer With Low to Intermediate HER2 Expression1
3CompletedPreventionIris Melanoma / Medium/Large Size Posterior Uveal Melanoma / Mucosal Melanoma / Ocular Melanoma With Extraocular Extension / Recurrent Melanoma / Recurrent Uveal Melanoma / Small Size Posterior Uveal Melanoma / Stage IIA Cutaneous Melanoma AJCC v6 and v7 / Stage IIA Uveal Melanoma AJCC v7 / Stage IIB Cutaneous Melanoma AJCC v6 and v7 / Stage IIB Uveal Melanoma AJCC v7 / Stage IIC Cutaneous Melanoma AJCC v6 and v7 / Stage IIIA Cutaneous Melanoma AJCC v7 / Stage IIIA Uveal Melanoma AJCC v7 / Stage IIIB Cutaneous Melanoma AJCC v7 / Stage IIIB Uveal Melanoma AJCC v7 / Stage IIIC Cutaneous Melanoma AJCC v7 / Stage IIIC Uveal Melanoma AJCC v7 / Stage IV Cutaneous Melanoma AJCC v6 and v7 / Stage IV Uveal Melanoma AJCC v71
3CompletedSupportive CareHead and Neck Carcinoma / Oral Complications / Radiation Toxicity1
3CompletedSupportive CareHead and Neck Carcinoma / Oral Mucositis / Radiation Toxicity / Tongue Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bayer Healthcare
  • Genzyme Inc.
  • Hospira Inc.
  • Kramer-Novis
  • Physicians Total Care Inc.
  • Wyeth Pharmaceuticals
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous; Subcutaneous250 ug/1mL
Injection, powder, for solutionSubcutaneous250 ug/1mL
Injection, powder, lyophilized, for solutionIntravenous; Subcutaneous250 ug/1mL
Injection, solutionIntravenous; Subcutaneous500 ug/1mL
LiquidIntravenous; Subcutaneous500 ug/1mL
LiquidSubcutaneous500 ug/1mL
Prices
Unit descriptionCostUnit
Leukine 250 mcg vial204.79USD vial
Bio-immunex capsule0.42USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA1341150No2000-12-052017-12-05Canada flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
isoelectric point5.05Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor activity
Specific Function
Low affinity receptor for granulocyte-macrophage colony-stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells.
Gene Name
CSF2RA
Uniprot ID
P15509
Uniprot Name
Granulocyte-macrophage colony-stimulating factor receptor subunit alpha
Molecular Weight
46206.185 Da
References
  1. Wang Y, Cai D, Brendel C, Barett C, Erben P, Manley PW, Hochhaus A, Neubauer A, Burchert A: Adaptive secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR/ABL+ progenitors via JAK-2/STAT-5 pathway activation. Blood. 2007 Mar 1;109(5):2147-55. Epub 2006 Nov 7. [Article]
  2. Chen J, Carcamo JM, Golde DW: The alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor interacts with c-Kit and inhibits c-Kit signaling. J Biol Chem. 2006 Aug 4;281(31):22421-6. Epub 2006 Jun 7. [Article]
  3. Lencz T, Morgan TV, Athanasiou M, Dain B, Reed CR, Kane JM, Kucherlapati R, Malhotra AK: Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia. Mol Psychiatry. 2007 Jun;12(6):572-80. Epub 2007 Mar 20. [Article]
  4. Xiao R, Zhang R, Wang YL, Zhu ZL, Chen T, Yang JH: [Expression of soluble GM-CSF-Ralpha in patients with acute myeloid leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2006 Apr;14(2):225-7. [Article]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Interleukin-3 receptor activity
Specific Function
This is a receptor for interleukin-3.
Gene Name
IL3RA
Uniprot ID
P26951
Uniprot Name
Interleukin-3 receptor subunit alpha
Molecular Weight
43329.585 Da
References
  1. Eksioglu EA, Mahmood SS, Chang M, Reddy V: GM-CSF promotes differentiation of human dendritic cells and T lymphocytes toward a predominantly type 1 proinflammatory response. Exp Hematol. 2007 Aug;35(8):1163-71. Epub 2007 Jun 11. [Article]
  2. Sakhno LV, Leplina OIu, Tikhonova MA, Raspai ZhM, Gileva IP, Nikonov SD, Zhdanov OA, Ostanin AA, Chernykh ER: [Characteristics of A-interferon-generated dendritic cells in patients with pulmonary tuberculosis]. Probl Tuberk Bolezn Legk. 2007;(3):42-6. [Article]
  3. Ward KA, Stewart LA, Schwarer AP: CD34+-derived CD11c+ + + BDCA-1+ + CD123+ + DC: expansion of a phenotypically undescribed myeloid DC1 population for use in adoptive immunotherapy. Cytotherapy. 2006;8(2):130-40. [Article]
  4. Lencz T, Morgan TV, Athanasiou M, Dain B, Reed CR, Kane JM, Kucherlapati R, Malhotra AK: Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia. Mol Psychiatry. 2007 Jun;12(6):572-80. Epub 2007 Mar 20. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor activity
Specific Function
High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor.
Gene Name
CSF2RB
Uniprot ID
P32927
Uniprot Name
Cytokine receptor common subunit beta
Molecular Weight
97334.89 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Shen Y, Baker E, Callen DF, Sutherland GR, Willson TA, Rakar S, Gough NM: Localization of the human GM-CSF receptor beta chain gene (CSF2RB) to chromosome 22q12.2-->q13.1. Cytogenet Cell Genet. 1992;61(3):175-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Pdz domain binding
Specific Function
Cell surface proteoglycan that bears heparan sulfate. Regulates dendritic arbor morphogenesis (By similarity).
Gene Name
SDC2
Uniprot ID
P34741
Uniprot Name
Syndecan-2
Molecular Weight
22159.62 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Modrowski D, Basle M, Lomri A, Marie PJ: Syndecan-2 is involved in the mitogenic activity and signaling of granulocyte-macrophage colony-stimulating factor in osteoblasts. J Biol Chem. 2000 Mar 31;275(13):9178-85. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Heparin binding
Specific Function
Cytotoxin and helminthotoxin. Also induces non-cytolytic histamine release from human basophils. Involved in antiparasitic defense mechanisms and immune hypersensitivity reactions. The proform acts...
Gene Name
PRG2
Uniprot ID
P13727
Uniprot Name
Bone marrow proteoglycan
Molecular Weight
25205.345 Da
References
  1. Menon K, Wu Y, Haas J, Sahu SK, Yang B, Zaheer A: Diminished degradation of myelin basic protein by anti-sulfatide antibody and interferon-gamma in myelin from glia maturation factor-deficient mice. Neurosci Res. 2007 Jun;58(2):156-63. Epub 2007 Feb 22. [Article]
  2. Letuve S, Lajoie-Kadoch S, Audusseau S, Rothenberg ME, Fiset PO, Ludwig MS, Hamid Q: IL-17E upregulates the expression of proinflammatory cytokines in lung fibroblasts. J Allergy Clin Immunol. 2006 Mar;117(3):590-6. Epub 2006 Feb 8. [Article]
  3. Kang JH, Lee da H, Seo H, Park JS, Nam KH, Shin SY, Park CS, Chung IY: Regulation of functional phenotypes of cord blood derived eosinophils by gamma-secretase inhibitor. Am J Respir Cell Mol Biol. 2007 Nov;37(5):571-7. Epub 2007 Jun 28. [Article]

Drug created on June 13, 2005 13:24 / Updated on May 21, 2021 10:20