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Identification
NameAnakinra
Accession NumberDB00026  (BIOD00060, BTD00060)
Typebiotech
Groupsapproved
Description

Anakinra is a recombinant, nonglycosylated human interleukin-1 receptor antagonist (IL-1Ra). The difference between anakinra and the native human IL-1Ra is that anakinra has an extra methionine residue at the amino terminus. It is manufactured by using the E. coli expression system. Anakinra is composed of 153 amino acid residues. FDA approved on November 14, 2001.

Protein structureDb00026
Protein chemical formulaC759H1186N208O232S10
Protein average weight17257.6000
Sequences
>DB00026 sequence
MRPSGRKSSKMQAFRIWDVNQKTFYLRNNQLVAGYLQGPNVNLEEKIDVVPIEPHALFLG
IHGGKMCLSCVKSGDETRLQLEAVNITDLSENRKQDKRFAFIRSDSGPTTSFESAACPGW
FLCTAMEADQPVSLTNMPDEGVMVTKFYFQEDE
Download FASTA Format
Synonyms
SynonymLanguageCode
ICIL-1RANot AvailableNot Available
IL-1raNot AvailableNot Available
IL-1RNNot AvailableNot Available
IL1 inhibitorNot AvailableNot Available
Interleukin-1 receptor antagonist protein precursorNot AvailableNot Available
IRAPNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
KineretAmgen Inc
Brand mixturesNot Available
Categories
CAS number143090-92-0
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor the treatment of adult rheumatoid arthritis and treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID).
PharmacodynamicsUsed to treat rheumatoid arthritis, Anakinra blocks the biologic activity of IL-1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. Patients with rheumatoid arthritis have elevated levels of IL-1. The levels of the naturally occurring IL-1Ra in synovium and synovial fluid from rheumatoid arthritis (RA) patients are not sufficient to compete with the elevated amount of locally produced IL-1. Increasing the levels of IL-1Ra by artificial means reduces the negative effects (cartilage degradation, bone resorption) of IL-1.
Mechanism of actionAnakinra binds competitively to the Interleukin-1 type I receptor (IL-1RI), thereby inhibiting the action of elevated levels IL-1 which normally can lead to cartilage degradation and bone resorption.
AbsorptionWhen a 70 mg subcutaneous bolus injection is given to healthy subjects, the absolute bioavailability is 95%. Accumulation does not occur following daily subcutaneous doses. Tmax, SubQ, 1-2 mg/kg, healthy subjects = 3-7 hours; Cmax, SubQ, 3 mg/kg once daily, NOMID patients = 3628 ng/mL.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeHealthy subjects = 4 - 6 hours; NOMID patients = 5.7 hours (range of 3.1 - 28.2 hours).
Clearance

Clearance is variable and increases with increasing creatinine clearance and body weight. However, gender and age were not significant factors.

ToxicityMost common adverse reactions (incidence ≥ 5%) are injection site reaction, worsening of rheumatoid arthritis, upper respiratory tract infection, headache, nausea, diarrhea, sinusitis, arthralgia, flu like-symptoms, and abdominal pain when anakinra is used in RA patients. In NOMID patients, the most common AEs during the first 6 months of treatment (incidence >10%) are injection site reaction, headache, vomiting, arthralgia, pyrexia, and nasopharyngitis.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous10MIU/VIAL; 18MIU/VIAL; 25MIU/VIAL
Prices
Unit descriptionCostUnit
Kineret 1 Box = 7 Syringes, 4.69ml Box449.9USDbox
Kineret 100 mg/0.67 ml syr61.8USDsyringe
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada21419532008-04-082013-09-17
Canada13413222001-11-272018-11-27
Properties
Stateliquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.412Not Available
isoelectric point5.46Not Available
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Lequerré T, Quartier P, Rosellini D, Alaoui F, De Bandt M, Mejjad O, Kone-Paut I, Michel M, Dernis E, Khellaf M, Limal N, Job-Deslandre C, Fautrel B, Le Loët X, Sibilia J; Société Francophone pour la Rhumatologie et les Maladies Inflammatoires en Pédiatrie (SOFREMIP); Club Rhumatismes et Inflammation (CRI): Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France. Ann Rheum Dis. 2008 Mar;67(3):281-2.
    Pubmed
  3. FDA label
External Links
ResourceLink
UniProtP18510
GenbankM55646
PharmGKBPA10799
Drug Product Database2245913
RxListhttp://www.rxlist.com/cgi/generic/anakinra.htm
Drugs.comhttp://www.drugs.com/cdi/anakinra.html
WikipediaAnakinra
ATC CodesL04AC03
AHFS Codes
  • 92:00.00
PDB Entries
FDA labelshow(62.3 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
Canakinumabresults in increased immunosuppressive effects; increases the risk of infection.
Certolizumab pegolCo-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
golimumabAvoid combination with anakinra due to the increased chance of serious infection.
Rilonaceptresults in increased immunosuppressive effects; increases the risk of infection.
ThalidomideThalidomide may increase the adverse effects of Anakinra. Increased risk of serious infection. Concomitant therapy should be avoided.
TofacitinibAvoid combination due to the potential increase in tofacitinib related adverse effects.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food InteractionsNot Available

1. Interleukin-1 receptor type 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Interleukin-1 receptor type 1 P14778 Details

References:

  1. Tang YH, Zhang SP, Liang Y, Deng CQ: [Effects of Panax notoginseng saponins on mRNA expressions of interleukin-1 beta, its correlative factors and cysteinyl-aspartate specific protease after cerebral ischemia-reperfusion in rats] Zhong Xi Yi Jie He Xue Bao. 2007 May;5(3):328-32. Pubmed
  2. Dayer JM: The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis. Rheumatology (Oxford). 2003 May;42 Suppl 2:ii3-10. Pubmed
  3. Vamvakopoulos J, Green C, Metcalfe S: Genetic control of IL-1beta bioactivity through differential regulation of the IL-1 receptor antagonist. Eur J Immunol. 2002 Oct;32(10):2988-96. Pubmed
  4. Do H, Vasilescu A, Carpentier W, Meyer L, Diop G, Hirtzig T, Coulonges C, Labib T, Spadoni JL, Therwath A, Lathrop M, Matsuda F, Zagury JF: Exhaustive genotyping of the interleukin-1 family genes and associations with AIDS progression in a French cohort. J Infect Dis. 2006 Dec 1;194(11):1492-504. Epub 2006 Oct 26. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  6. So A, De Smedt T, Revaz S, Tschopp J: A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther. 2007;9(2):R28. Pubmed
  7. Vannier E, Kaser A, Atkins MB, Fantuzzi G, Dinarello CA, Mier JW, Tilg H: Elevated circulating levels of soluble interleukin-1 receptor type II during interleukin-2 immunotherapy. Eur Cytokine Netw. 1999 Mar;10(1):37-42. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on June 19, 2013 20:10