DrugBank: Sargramostim (DB00020)

targets (5)

Identification

Name

Sargramostim

Accession Number

DB00020 (BIOD00035, BTD00035)

Type

biotech

Groups

approved

Description

Human, recombinant GM-CSF, expressed in yeast. Glycoprotein that is 127 residues. Substitution of Leu23 leads to a difference from native protein.

Protein structure

Display: 3D Structure

Protein chemical formula

C₆₃₉H₁₀₀₆N₁₆₈O₁₉₆S₈

Protein average weight

14434.5000

Sequences

>DB00020 sequence
APARSPSPSTQPWEHVNAIQEALRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE
LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD
CWEPVQE

FASTA

Synonyms

Colony-stimulating factor
CSF
GM-CSF
Granulocyte-macrophage colony-stimulating factor precursor
Molgramostin

Salts

Not Available

Brand names

Name	Company
Immunex
Leucomax (Novartis)
Leukine
Leukine (Berlex Laboratories Inc)

Brand mixtures

Not Available

Categories

Antineoplastic Agents
Immunomodulatory Agents
Anti-Infective Agents

CAS number

83869-56-1

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

For the treatment of cancer and bone marrow transplant

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

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)]

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Form	Route	Strength
Injection, powder, for solution	Intravenous drip
Injection, powder, for solution	Subcutaneous
Injection, solution	Intravenous drip
Injection, solution	Subcutaneous

Prices

Unit description	Cost	Unit
Leukine 250 mcg vial	204.79 USD	vial
Bio-immunex capsule	0.42 USD	capsule

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Country	Patent Number	Approved	Expires (estimated)
Canada	1341150	2000-12-05	2017-12-05

Properties

State

liquid

Experimental Properties

Property	Value	Source
isoelectric point	5.05	Not Available

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
UniProt	P04141
Genbank	M13207
PharmGKB	PA164748631
RxList	http://www.rxlist.com/cgi/generic/sargramostim.htm
Drugs.com	http://www.drugs.com/cdi/sargramostim.html
Wikipedia	http://en.wikipedia.org/wiki/Sargramostim

ATC Codes

L03AA09

AHFS Codes

Not Available

PDB Entries

2GMF

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Granulocyte-macrophage colony-stimulating factor receptor alpha chain Pharmacological action: yes Actions: agonist Low affinity receptor for granulocyte-macrophage colony- stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells Organism class: human UniProt ID: P15509 Gene: CSF2RA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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. Pubmed 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. Pubmed 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. Pubmed 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. Pubmed Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed 2. Interleukin-3 receptor alpha chain Pharmacological action: yes Actions: agonist This is a receptor for interleukin-3 Organism class: human UniProt ID: P26951 Gene: IL3RA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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. Pubmed 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. Pubmed 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. Pubmed 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. Pubmed 3. Cytokine receptor common beta chain Pharmacological action: yes Actions: agonist High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor Organism class: human UniProt ID: P32927 Gene: CSF2RB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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. Pubmed 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. Pubmed 4. Syndecan-2 Pharmacological action: unknown Actions: agonist Cell surface proteoglycan that bears heparan sulfate Organism class: human UniProt ID: P34741 Gene: SDC2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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. Pubmed 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. Pubmed 5. Bone-marrow proteoglycan Pharmacological action: unknown Cytotoxin and helminthotoxin. Also induces non-cytolytic histamine release from human basophils. Involved in antiparasitic defense mechanisms and immune hypersensitivity reactions. The proform acts as a proteinase inhibitor, reducing the activity of PAPPA Organism class: human UniProt ID: P13727 Gene: PRG2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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. Pubmed 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. Pubmed Kang JH, Lee DH, Seo HM, 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 Jun 28;. Pubmed

Targets

1. Granulocyte-macrophage colony-stimulating factor receptor alpha chain

Pharmacological action: yes
Actions: agonist

Low affinity receptor for granulocyte-macrophage colony- stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells

Organism class: human
UniProt ID: P15509 Link_out

Gene: CSF2RA Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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. Pubmed
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. Pubmed
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. Pubmed
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. Pubmed
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Interleukin-3 receptor alpha chain

Pharmacological action: yes
Actions: agonist

This is a receptor for interleukin-3

Organism class: human
UniProt ID: P26951 Link_out

Gene: IL3RA Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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. Pubmed
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. Pubmed
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. Pubmed
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. Pubmed

3. Cytokine receptor common beta chain

Pharmacological action: yes
Actions: agonist

High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor

Organism class: human
UniProt ID: P32927 Link_out

Gene: CSF2RB Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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. Pubmed
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. Pubmed

4. Syndecan-2

Pharmacological action: unknown
Actions: agonist

Cell surface proteoglycan that bears heparan sulfate

Organism class: human
UniProt ID: P34741 Link_out

Gene: SDC2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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. Pubmed
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. Pubmed

5. Bone-marrow proteoglycan

Pharmacological action: unknown

Cytotoxin and helminthotoxin. Also induces non-cytolytic histamine release from human basophils. Involved in antiparasitic defense mechanisms and immune hypersensitivity reactions. The proform acts as a proteinase inhibitor, reducing the activity of PAPPA

Organism class: human
UniProt ID: P13727 Link_out

Gene: PRG2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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. Pubmed
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. Pubmed
Kang JH, Lee DH, Seo HM, 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 Jun 28;. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on October 31, 2010 08:54