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Identification
NameEtanercept
Accession NumberDB00005  (BIOD00052, BTD00052)
TypeBiotech
GroupsApproved, Investigational
Description

Dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton (p75) tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. The Fc component of etanercept contains the CH2 domain, the CH3 domain and hinge region, but not the CH1 domain of IgG1. Etanercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian cell expression system. It consists of 934 amino acids

Protein structureDb00005
Protein chemical formulaC2224H3475N621O698S36
Protein average weight51234.9 Da
Sequences
> Etanercept Sequence
LPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPGQHAKVFCTKTSDTVCDSCEDST
YTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTCRPGWYCALSKQEGCRLCAPLRK
CRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICRPHQICNVVAIPGNASMDAVCTS
TSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTSFLLPMGPSPPAEGSTGDEPKSC
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD
GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA Format
Synonyms
CD120b
p75
p80 TNF-alpha receptor
TNF-R2
Tumor necrosis factor receptor 2
Tumor necrosis factor receptor superfamily member 1B precursor
Tumor necrosis factor receptor type II
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EnbrelkitImmunex Corporation2003-01-02Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Enbrelsolution50 mgsubcutaneousImmunex Corporation2005-12-21Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Enbrelsolution25 mg/.5mLsubcutaneousImmunex Corporation2005-11-10Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Enbrelsolution50 mg/mLsubcutaneousImmunex Corporation2005-11-10Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Enbrelsolution50 mg/mLsubcutaneousImmunex Corporation2005-10-06Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
Enbrel SureclickNot Available
Brand mixtures
NameLabellerIngredients
EnbrelImmunex Corporation
SaltsNot Available
Categories
CAS number185243-69-0
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor treatment of severe active rheumatoid arthritis in adults, severe juvenile idiopathic arthritis, ankylosing spondylitis, and severe plaque psoriasis.
PharmacodynamicsTumor necrosis factor TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF are found in tissues and fluids of patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (AS), and plaque psoriasis. Etanercept binds specifically to tumor necrosis factor (TNF) and blocks its interaction with cell surface TNF receptors.
Mechanism of actionThere are two distinct receptors for TNF (TNFRs), a 55 kilodalton protein (p55) and a 75 kilodalton protein (p75). The biological activity of TNF is dependent upon binding to either cell surface receptor (p75 or p55). Etanercept is a dimeric soluble form of the p75 TNF receptor that can bind to two TNF molecules, thereby effectively removing them from circulation.
AbsorptionBioavailability following sub-Q administration is approximately 60%. Peak plasma concentrations achieved within 69 hours.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life102 +/- 30 hrs in individuals with rheumatoid arthritis and 68 hours in healthy adults
Clearance
  • 160 +/- 80 mL/hr [RA patients]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
Manufacturers
  • Amgen Inc. + Wyeth + Takeda
Packagers
Dosage forms
FormRouteStrength
Kit
Kit; liquid; powder for solutionsubcutaneous
Solutionsubcutaneous25 mg/.5mL
Solutionsubcutaneous50 mg/mL
Solutionsubcutaneous50 mg
Prices
Unit descriptionCostUnit
Enbrel (1 Box = 1 Kit = Four 50 mg Syringes) 3.92ml Box2033.14USD box
Enbrel SureClick (1 Box Contains Four 50 mg Prefilled Autoinjectors)2033.14USD box
Enbrel 4 25 mg Kit (1 Box = 1 Kit = Four 25 mg Vials)1016.57USD box
Enbrel 50 mg/ml sureclick syr488.74USD syringe
Enbrel 25 mg kit250.37USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada21235932000-03-142013-09-14
Canada24769342009-06-162023-02-27
United States367552000-06-272012-10-23
United States72764772007-10-022024-07-29
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity-0.529Not Available
isoelectric point7.89Not Available
References
Synthesis Reference

Timothy D. Osslund, Christi L. Clogston, Shon Lee Crampton, Randal B. Bass, “Crystals of etanercept and methods of making thereof.” U.S. Patent US07276477, issued October 02, 2007.

US07276477
General References
  1. http://www.genome.jp/dbget-bin/www_bget?D00742
    #American Society of Health System Pharmacists, Inc., DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995. Etanercept; [updated 2014 Sept 24 cited 2014 Nov 11]. Available from http://web.b.ebscohost.com.login.ezproxy.library.ualberta.ca/dynamed/detail?vid=4&sid=eeea413d-1490-4efa-bf5d-71f40e1986a1%40sessionmgr111&hid=123&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#db=dme&AN=232781
External Links
ATC CodesL04AB01
AHFS Codes
  • 92:00.00
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AbataceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Abatacept.
AnakinraThe risk or severity of adverse effects can be increased when Etanercept is combined with Anakinra.
BelimumabThe risk or severity of adverse effects can be increased when Etanercept is combined with Belimumab.
CanakinumabThe risk or severity of adverse effects can be increased when Etanercept is combined with Canakinumab.
Certolizumab pegolEtanercept may increase the immunosuppressive activities of Certolizumab pegol.
CyclophosphamideThe risk or severity of adverse effects can be increased when Etanercept is combined with Cyclophosphamide.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Etanercept.
InfliximabEtanercept may increase the immunosuppressive activities of Infliximab.
LeflunomideThe risk or severity of adverse effects can be increased when Etanercept is combined with Leflunomide.
NatalizumabThe risk or severity of adverse effects can be increased when Etanercept is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Etanercept.
Rabies vaccineThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Etanercept.
RilonaceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Rilonacept.
RoflumilastRoflumilast may increase the immunosuppressive activities of Etanercept.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Etanercept.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Etanercept.
TocilizumabTocilizumab may increase the immunosuppressive activities of Etanercept.
TofacitinibThe risk or severity of adverse effects can be increased when Etanercept is combined with Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Etanercept.
VedolizumabThe risk or severity of adverse effects can be increased when Etanercept is combined with Vedolizumab.
Food InteractionsNot Available

Targets

1. Tumor necrosis factor

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: antibody

Components

Name UniProt ID Details
Tumor necrosis factor P01375 Details

References:

  1. Park YC, Burkitt V, Villa AR, Tong L, Wu H: Structural basis for self-association and receptor recognition of human TRAF2. Nature. 1999 Apr 8;398(6727):533-8. Pubmed
  2. Sandborn WJ, Hanauer SB: Antitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, pharmacology, clinical results, and safety. Inflamm Bowel Dis. 1999 May;5(2):119-33. Pubmed
  3. Grell M, Zimmermann G, Gottfried E, Chen CM, Grunwald U, Huang DC, Wu Lee YH, Durkop H, Engelmann H, Scheurich P, Wajant H, Strasser A: Induction of cell death by tumour necrosis factor (TNF) receptor 2, CD40 and CD30: a role for TNF-R1 activation by endogenous membrane-anchored TNF. EMBO J. 1999 Jun 1;18(11):3034-43. Pubmed
  4. Moreland LW: Inhibitors of tumor necrosis factor: new treatment options for rheumatoid arthritis. Cleve Clin J Med. 1999 Jun;66(6):367-74. Pubmed
  5. Calabrese LH: Rheumatoid arthritis and primary care: the case for early diagnosis and treatment. J Am Osteopath Assoc. 1999 Jun;99(6):313-21. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Tumor necrosis factor receptor superfamily member 1B

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tumor necrosis factor receptor superfamily member 1B P20333 Details

References:

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

3. High affinity immunoglobulin gamma Fc receptor I

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
High affinity immunoglobulin gamma Fc receptor I P12314 Details

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. Pubmed
  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. Pubmed

4. Low affinity immunoglobulin gamma Fc region receptor III-A

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor III-A P08637 Details

References:

  1. Criswell LA, Lum RF, Turner KN, Woehl B, Zhu Y, Wang J, Tiwari HK, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL Jr: The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis Rheum. 2004 Sep;50(9):2750-6. Pubmed
  2. Hughes LB, Criswell LA, Beasley TM, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL: Genetic risk factors for infection in patients with early rheumatoid arthritis. Genes Immun. 2004 Dec;5(8):641-7. Pubmed

5. Low affinity immunoglobulin gamma Fc region receptor II-a

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-a P12318 Details

References:

  1. Criswell LA, Lum RF, Turner KN, Woehl B, Zhu Y, Wang J, Tiwari HK, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL Jr: The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis Rheum. 2004 Sep;50(9):2750-6. Pubmed
  2. Hughes LB, Criswell LA, Beasley TM, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL: Genetic risk factors for infection in patients with early rheumatoid arthritis. Genes Immun. 2004 Dec;5(8):641-7. Pubmed

6. Low affinity immunoglobulin gamma Fc region receptor II-b

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-b P31994 Details

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. Pubmed
  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. Pubmed

7. Low affinity immunoglobulin gamma Fc region receptor II-c

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-c P31995 Details

References:

  1. Hart SP, Ross JA, Ross K, Haslett C, Dransfield I: Molecular characterization of the surface of apoptotic neutrophils: implications for functional downregulation and recognition by phagocytes. Cell Death Differ. 2000 May;7(5):493-503. Pubmed
  2. Ranheim EA, Kipps TJ: Tumor necrosis factor-alpha facilitates induction of CD80 (B7-1) and CD54 on human B cells by activated T cells: complex regulation by IL-4, IL-10, and CD40L. Cell Immunol. 1995 Apr 1;161(2):226-35. Pubmed

8. Lymphotoxin-alpha

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Lymphotoxin-alpha P01374 Details

References:

  1. Johnson CJ, Reilly KM, Murray KM: Etanercept in juvenile rheumatoid arthritis. Ann Pharmacother. 2001 Apr;35(4):464-71. Pubmed
  2. Pennica D, Lam VT, Mize NK, Weber RF, Lewis M, Fendly BM, Lipari MT, Goeddel DV: Biochemical properties of the 75-kDa tumor necrosis factor receptor. Characterization of ligand binding, internalization, and receptor phosphorylation. J Biol Chem. 1992 Oct 15;267(29):21172-8. Pubmed
  3. Gudbrandsdottir S, Larsen R, Sorensen LK, Nielsen S, Hansen MB, Svenson M, Bendtzen K, Muller K: TNF and LT binding capacities in the plasma of arthritis patients: effect of etanercept treatment in juvenile idiopathic arthritis. Clin Exp Rheumatol. 2004 Jan-Feb;22(1):118-24. Pubmed
  4. Buch MH, Conaghan PG, Quinn MA, Bingham SJ, Veale D, Emery P: True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin alpha? Ann Rheum Dis. 2004 Oct;63(10):1344-6. Epub 2004 Mar 19. Pubmed
  5. Kang CP, Lee KW, Yoo DH, Kang C, Bae SC: The influence of a polymorphism at position -857 of the tumour necrosis factor alpha gene on clinical response to etanercept therapy in rheumatoid arthritis. Rheumatology (Oxford). 2005 Apr;44(4):547-52. Epub 2005 Feb 3. Pubmed

9. Low affinity immunoglobulin gamma Fc region receptor III-B

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor III-B O75015 Details

References:

  1. Hart SP, Ross JA, Ross K, Haslett C, Dransfield I: Molecular characterization of the surface of apoptotic neutrophils: implications for functional downregulation and recognition by phagocytes. Cell Death Differ. 2000 May;7(5):493-503. Pubmed
  2. Ozgocmen S, Godekmerdan A, Ozkurt-Zengin F: Acute-phase response, clinical measures and disease activity in ankylosing spondylitis. Joint Bone Spine. 2007 May;74(3):249-53. Epub 2007 Mar 5. Pubmed
  3. Criswell LA, Lum RF, Turner KN, Woehl B, Zhu Y, Wang J, Tiwari HK, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL Jr: The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis Rheum. 2004 Sep;50(9):2750-6. Pubmed
  4. Hughes LB, Criswell LA, Beasley TM, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL: Genetic risk factors for infection in patients with early rheumatoid arthritis. Genes Immun. 2004 Dec;5(8):641-7. Pubmed

10. Complement C1s subcomponent

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1s subcomponent P09871 Details

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. Pubmed
  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. Pubmed

11. Complement C1r subcomponent

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1r subcomponent P00736 Details

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. Pubmed
  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. Pubmed

12. Complement C1q subcomponent subunit A

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit A P02745 Details

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. Pubmed
  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. Pubmed

13. Complement C1q subcomponent subunit B

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit B P02746 Details

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. Pubmed
  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. Pubmed

14. Complement C1q subcomponent subunit C

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit C P02747 Details

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. Pubmed
  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. Pubmed

Enzymes

1. Prostaglandin G/H synthase 2

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Bawolak MT, Touzin K, Moreau ME, Desormeaux A, Adam A, Marceau F: Cardiovascular expression of inflammatory signaling molecules, the kinin B1 receptor and COX2, in the rabbit: effects of LPS, anti-inflammatory and anti-hypertensive drugs. Regul Pept. 2008 Feb 7;146(1-3):157-68. Epub 2007 Sep 14. Pubmed
  2. Genovese T, Mazzon E, Crisafulli C, Di Paola R, Muia C, Bramanti P, Cuzzocrea S: Immunomodulatory effects of etanercept in an experimental model of spinal cord injury. J Pharmacol Exp Ther. 2006 Mar;316(3):1006-16. Epub 2005 Nov 22. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on November 11, 2014 14:53