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Showing drug card for Glatiramer Acetate (DB05259)

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Version 2.5
Creation Date 2007-11-18 18:22:49
Update Date 2009-02-19 16:03:37
Primary Accession Number DB05259
Secondary Accession Number
  • APRD00999
Name Glatiramer Acetate
Drug Type
  • Approved
  • Biotech
  • Investigational
Description Glatiramer acetate consists of the acetate salts of synthetic polypeptides, containing four naturally occurring amino acids: L-glutamic acid, L-alanine, L-tyrosine, and L-lysine with an average molar fraction of 0.141, 0.427, 0.095, and 0.338, respectively. The average molecular weight of glatiramer acetate is 5,000-9,000 daltons. It is an immunomodulator, licensed in much of the world for reduced frequency of relapses in relapsing-remitting multiple sclerosis
Synonyms
  1. COP-1
  2. Copolymer-1
  3. Copoylmer 1
  4. glatiramer acetate
Brand Names
  1. Copaxone
Brand Mixtures Not Available
Chemical IUPAC Name acetic acid; (2S)-2-amino-3-(4-hydroxyphenyl)propanoic acid; (2S)-2-aminopentanedioic acid; (2S)-2-aminopropanoic acid; (2S)-2,6-diaminohexanoic acid
Chemical Formula C25H45N5O13
Chemical Structure Structure
Protein Sequence(s) Not Available
CAS Registry Number 147245-92-9
InChI Identifier InChI=1/C9H11NO3.C6H14N2O2.C5H9NO4.C3H7NO2.C2H4O2/c10-8(9(12)13)5-6-1-3-7(11)4-2-6;7-4-2-1-3-5(8)6(9)10;6-3(5(9)10)1-2-4(7)8;1-2(4)3(5)6;1-2(3)4/h1-4,8,11H,5,10H2,(H,12,13);5H,1-4,7-8H2,(H,9,10);3H,1-2,6H2,(H,7,8)(H,9,10);2H,4H2,1H3,(H,5,6);1H3,(H,3,4)/t8-;5-;3-;2-;/m0000./s1/f/h12H;9H;7,9H;5H;3H
InChI Key FHEAIOHRHQGZPC-KEIVEFADDQ
KEGG Drug Not Available
KEGG Compound Not Available
PubChem Compound 3081884 Link Image
PubChem Substance 14863134 Link Image
ChEBI ID Not Available
PharmGKB ID PA449760 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02233014 Link Image
RxList Link http://www.rxlist.com/cgi/generic/glatiramer.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Glatiramer_acetate Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 623.6505
Monoisotopic Molecular Weight 623.3014
State Liquid
Melting Point Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility Not Available Calculated using ALOGPS
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP Not Available Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS Not Available Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.N[C@@H](CCC(O)=O)C(O)=O.N[C@@H](CC1=CC=C(O)C=C1)C(O)=O
Canonical SMILES CC(O)=O.CC(N)C(O)=O.NCCCCC(N)C(O)=O.NC(CCC(O)=O)C(O)=O.NC(CC1=CC=C(O)C=C1)C(O)=O
Drug Category
  • Adjuvants, Immunologic
  • Immunosuppressive Agents
ATC Codes Not Available
AHFS Codes Not Available
Indication For reduction of the frequency of relapses in patients with Relapsing-Remitting Multiple Sclerosis.
Pharmacology Glatiramer acetate was originally designed to mimic a protein in myelin, called myelin basic protein, with the intention of inducing EAE (an animal model of MS). Quite to the contrary, it was found to suppress the disease and as a result came to be trialed in human MS. There is some evidence that Glatiramer acetate converts the body's immune response from a Th1 type to a Th2 one, promotes suppressor T cells or acts as an altered peptide ligand. Studies in animals and in vitro systems suggest that upon its administration, glatiramer acetate-specific suppressor T-cells are induced and activated in the periphery. Some fraction of the injected material, either intact or partially hydrolyzed, is presumed to enter the lymphatic circulation, enabling it to reach regional lymph nodes, and some may enter the systemic circulation intact.
Mechanism of Action Glatiramer acetate (GA) exhibits strong and promiscuous binding to MHC molecules (HLA DRB1* variants) and consequent competition with various myelin antigens for their presentation to T cells. A further aspect of its action is potent induction of specific suppressor cells of the T helper 2 (Th2) type that migrate to the brain and lead to in situ bystander suppression. Furthermore, the GA-specific cells in the brain express the anti-inflammatory cytokines IL-10 and transforming growth factor beta, in addition to brain-derived neurotrophic factor, whereas they do not express the inflammatory cytokine IFN-gamma. Recent evidence also suggests that Glatiramer acetate directly inhibits dendritic cells and monocytes - both of which are circulating antigen presenting cells.
Absorption Not Available
Toxicity Adverse reactions include injection site reactions, vasodilatation, chest pain, asthenia, infection, pain, nausea, arthralgia, anxiety, and hypertonia.
Protein Binding Not Available
Biotransformation Hydrolyzed by proteases
Half Life Not Available
Dosage Forms
Form Route
Powder, for solution Subcutaneous
Solution Subcutaneous
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Francis DA: Glatiramer acetate (Copaxone). Int J Clin Pract. 2001 Jul-Aug;55(6):394-8. [PubMed Link Image]
  2. Arnon R, Aharoni R: Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications. Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14593-8. Epub 2004 Sep 15. [PubMed Link Image]
  3. Weber MS, Hohlfeld R, Zamvil SS: Mechanism of action of glatiramer acetate in treatment of multiple sclerosis. Neurotherapeutics. 2007 Oct;4(4):647-53. [PubMed Link Image]
  4. Li Q, Milo R, Panitch H, Swoveland P, Bever CT Jr: Glatiramer acetate blocks the activation of THP-1 cells by interferon-gamma. Eur J Pharmacol. 1998 Jan 26;342(2-3):303-10. [PubMed Link Image]
  5. Drugs.com Link Image
  6. Wikipedia Link Image
  7. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. HLA class II histocompatibility antigen, DRB1-1 beta chain
Drug Target 1 [top]
Target 1 ID 4183
Target 1 Name HLA class II histocompatibility antigen, DRB1-1 beta chain
Target 1 Synonyms
  1. DR-1
  2. DR1
  3. HLA class II histocompatibility antigen, DRB1-1 beta chain precursor
  4. MHC class I antigen DRB1*1
Target 1 Gene Name HLA-DRB1
Target 1 Protein Sequence >HLA class II histocompatibility antigen, DRB1-1 beta chain 
MVCLKLPGGSCMTALTVTLMVLSSPLALAGDTRPRFLWQLKFECHFFNGTERVRLLERCI
YNQEESVRFDSDVGEYRAVTELGRPDAEYWNSQKDLLEQRRAAVDTYCRHNYGVGESFTV
QRRVEPKVTVYPSKTQPLQHHNLLVCSVSGFYPGSIEVRWFRNGQEEKAGVVSTGLIQNG
DWTFQTLVMLETVPRSGEVYTCQVEHPSVTSPLTVEWRARSESAQSKMLSGVGGFVLGLL
FLGAGLFIYFRNQKGHSGLQPTGFLS
Target 1 Number of Residues 270
Target 1 Molecular Weight 29914
Target 1 Theoretical pI 7.78
Target 1 GO Classification
Function
Not Available
Process
response to stimulus
response to biotic stimulus
defense response
immune response
Component
cell
membrane
Target 1 General Function Not Available
Target 1 Specific Function Not Available
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-29
Target 1 Transmembrane Regions
  • 228-250
Target 1 Essentiality Non Essential
Target 1 GenBank ID Protein Not Available
Target 1 UniProtKB/Swiss-Prot ID P04229 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name 2B11_HUMAN Link Image
Target 1 PDB ID 1AQD Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Membrane
Target 1 Gene Sequence >801 bp 
ATGGTGTGTCTGAAGCTCCCTGGAGGCTCCTGCATGACAGCGCTGACAGTGACACTGATG
GTGCTGAGCTCCCGACTGGCTTTGGCTGGGGACACCCGACCACGTTTCTTGTGGCAGCTT
AAGTTTGAATGTCATTTCTTCAATGGGACGGAGCGGGTGCGGTTGCTGGAAAGATGCATC
TATAACCAAGAGGAGTCCGTGCGCTTCGACAGCGACGTGGGGGAGTACCGGGCGGTTGAG
GAGCTGGGGCGGCCTGATGCCGAGTACTGGAACAGCCAGAAGGACCTCCTGGAGCAGAAG
CGGGGCCAGGTGGACAATTACTGCAGACACAACTACGGGGTTGGTGAGAGCTTCACAGTG
CAGCGGCGAGTTGAGCCTAAGGTGACTGTGTATCCTTCAAAGACCCAGCCCCTGCAGCAC
CACAACCTCCTGGTCTGCTCTGTGAGTGGTTTCTATCCAGGCAGCATTGAAGTCAGGTGG
TTCCGGAACGGCCAGGAAGAGAAGGCTGGGGTGGTGTCCACGGGCCTGATCCAGAATGGA
GATTGGACCTTCCAGACCCTGGTGATGCTGGAAATAGTTCCTCGGAGTGGAGAGGTTTAC
ACCTGCCAAGTGGAGCACCCAAGTGTGACGAGCCCTCTCACAGTGGAATGGAGAGCACGG
TCTGAATCTGCACAGAGCAAGATGCTGAGTGGAGTCGGGGGCTTCGTGCTGGGCCTGCTC
TTCCTTGGGGCCGGGCTGTTCATCTACTTCAGGAATCAGAAAGGACACTCTGGACTTCAG
CCAACAGGATTCCTGAGCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID HLA-DRB1 Link Image
Target 1 HGNC ID HGNC:4948 Link Image
Target 1 Chromosome Location 6
Target 1 Locus 6p21.3
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Palou E, Mongay L, Arias MT, Isart F, Suarez B, Masso M, Fabregat V, Martorell J, Gaya A: Identification of a novel DRB1-allele (DRB1*0106) by sequence-based typing. Tissue Antigens. 1999 Mar;53(3):308-10. [PubMed Link Image]
  2. Coppin HL, Avoustin P, Fabron J, Huchenq A, Garnier JM, Thomsen M, De Preval C: Evolution of the HLA-DR1 gene family. Structural and functional analysis of the new allele "DR-BON". J Immunol. 1990 Feb 1;144(3):984-9. [PubMed Link Image]
  3. Hurley CK, Ziff BL, Silver J, Gregersen PK, Hartzman R, Johnson AH: Polymorphism of the HLA-DR1 haplotype in American blacks. Identification of a DR1 beta-chain determinant recognized in the mixed lymphocyte reaction. J Immunol. 1988 Jun 1;140(11):4019-23. [PubMed Link Image]
  4. Tonnelle C, DeMars R, Long EO: DO beta: a new beta chain gene in HLA-D with a distinct regulation of expression. EMBO J. 1985 Nov;4(11):2839-47. [PubMed Link Image]
  5. Bell JI, Estess P, St John T, Saiki R, Watling DL, Erlich HA, McDevitt HO: DNA sequence and characterization of human class II major histocompatibility complex beta chains from the DR1 haplotype. Proc Natl Acad Sci U S A. 1985 May;82(10):3405-9. [PubMed Link Image]
  6. Louis P, Eliaou JF, Kerlan-Candon S, Pinet V, Vincent R, Clot J: Polymorphism in the regulatory region of HLA-DRB genes correlating with haplotype evolution. Immunogenetics. 1993;38(1):21-6. [PubMed Link Image]
Target 1 Drug References
  1. Arnon R, Aharoni R: Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications. Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14593-8. Epub 2004 Sep 15. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.