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Identification
NameCanakinumab
Accession NumberDB06168
Typebiotech
Groupsapproved, investigational
Description

Canakinumab is a recombinant, human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/κ isotype subclass. It is expressed in a murine Sp2/0-Ag14 cell line and comprised of two 447- (or 448-) residue heavy chains and two 214-residue light chains, with a molecular mass of 145157 Daltons when deglycosylated. Both heavy chains of canakinumab contain oligosaccharide chains linked to the protein backbone at asparagine 298 (Asn 298). Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1alpha or IL-1 receptor antagonist (IL-1ra). Canakinumab is marketed under the brand name Ilaris and indicated for patients 4 years of age and older to treat Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), which are both part of the Cryopyrin-Associated Periodic Syndromes (CAPS) as well as for patients 2 years of age and older to treat systemic juvenile idiopathic arthritis (SJIA). Clinical trials have established the administration of canakinumab every 2 weeks to be safe and effective, offering a considerable advantage over the existing treatment with the human IL-1 receptor antagonist, anakinra, which must be injected daily and which is often poorly tolerated by patients.

Protein structureNo structure small
Protein chemical formulaC6452H9958N1722O2010S42
Protein average weight145200.0000
Sequences
>8836_H|canakinumab|Homo sapiens||H-GAMMA-1 (VH(1-118)+CH1(119-216)+HINGE-REGION(217-231)+CH2(232-341)+CH3(342-448))|||||||448||||MW 49253.6|MW 49253.6|
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVAIIWYDGDNQYY
ADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARDLRTGPFDYWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGK
>8836_L|canakinumab|Homo sapiens||L-KAPPA (V-KAPPA(1-107)+C-KAPPA(108-214))|||||||214||||MW 23357.9|MW 23357.9|
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVAIIWYDGDNQYY
ADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARDLRTGPFDYWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQSFSGVPS
RFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPFTFGPGTKVDIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
SynonymLanguageCode
ACZ-885Not AvailableNot Available
ACZ885Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
IlarisNovartis
Brand mixturesNot Available
CategoriesNot Available
CAS number914613-48-2
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
IndicationUsed in patients 4 years of age and older to treat Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), which are both part of the Cryopyrin-Associated Periodic Syndromes (CAPS) as well as for patients 2 years of age and older to treat systemic juvenile idiopathic arthritis (SJIA).
PharmacodynamicsNovartis AG has developed canakinumab as a subcutaneous injection and fully human mAb that neutralizes the bioactivity of human IL-1beta, which is involved in several inflammatory disorders. Canakinumab has promising clinical safety and pharmacokinetic properties, and demonstrated potential for the treatment of cryopyrin-associated periodic syndromes (CAPS), systemic juvenile idiopathic arthritis (SJIA), and possibly for other complex inflammatory diseases, such as rheumatoid arthritis, COPD disease and ocular diseases.
Mechanism of actionIn inflammatory diseases involving Cryopyrin-Associated Periodic Syndromes (CAPS), interleukin-1 beta (IL-1β) is excessively activated and drives inflammation. The protein cryopyrin controls the activation of IL-1β, and mutations in cryopyrin's gene, NLRP-3, up-regulate IL-1β activation. Canakinumab is a human monoclonal anti-human IL-1β antibody of the IgG1/κ isotype. Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1α or IL-1 receptor antagonist (IL-1ra).
AbsorptionThe absolute bioavailability of subcutaneous canakinumab is estimated to be 70%.
Volume of distribution
  • 6.01 L [typical CAPS patient weighing 70 kg]
Protein bindingCanakinumab binds to plasma IL-1β, but plasma protein binding was not quantified.
Metabolism

The metabolism of canakinumab is not yet determined.

Route of eliminationThe route of elimination for canakinumab has not yet been determined.
Half life26 days
Clearance
  • 0.174 L/day [typical CAPS patient weighing 70 kg]
ToxicityThe most common adverse reactions involved the central nervous system (headache and vertigo), gastrointestinal system (diarrhea and nausea), neuromuscular and skeletal system (musculoskeletal pain), and respiratory system (rhinitis, nasopharyngitis and bronchitis). Influenza was also reported.
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
Manufacturers
  • Novartis pharmaceuticals corp
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous150mg/mL
PricesNot Available
PatentsNot Available
Properties
Stateliquid
Experimental PropertiesNot Available
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Church LD, McDermott MF: Canakinumab, a fully-human mAb against IL-1beta for the potential treatment of inflammatory disorders. Curr Opin Mol Ther. 2009 Feb;11(1):81-9. Pubmed
  2. IMGT Link
  3. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN: Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009 Jun 4;360(23):2416-25. Pubmed
  4. FDA label.
External Links
ResourceLink
RxListhttp://www.rxlist.com/ilaris-drug.htm
Drugs.comhttp://www.drugs.com/mtm/canakinumab.html
WikipediaCanakinumab
ATC CodesL04AC08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(120 KB)
MSDSshow(568 KB)
Interactions
Drug Interactions
Drug
AdalimumabIncreases immunosuppressive effects and risk of infection.
AlefaceptIncreases immunosuppressive effects and risk of infection.
Anakinraresults in increased immunosuppressive effects; increases the risk of infection.
Antithymocyte globulinresults in increased immunosuppressive effects; increases the risk of infection.
Azathioprineresults in increased immunosuppressive effects; increases the risk of infection.
Basiliximabresults in increased immunosuppressive effects; increases the risk of infection.
golimumabAvoid combination with canakinumab due to the increased chance of neutropenia and/or serious infection.
NatalizumabAvoid combination due to the increased risk of infection.
PimecrolimusAvoid combination due the potential increase in immunosuppressant adverse effects.
Rilonaceptresults in increased immunosuppressive effects; increases the risk of infection.
TofacitinibAvoid combination with tofacitinib and other potent immunosuppressants due to potential enhancement of immunosuppressant effects.
Food Interactions
  • No food effects were found.

1. Interleukin-1 beta

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: binder

Components

Name UniProt ID Details
Interleukin-1 beta P01584 Details

References:

  1. Church LD, McDermott MF: Canakinumab, a fully-human mAb against IL-1beta for the potential treatment of inflammatory disorders. Curr Opin Mol Ther. 2009 Feb;11(1):81-9. Pubmed

Comments
Drug created on March 19, 2008 10:15 / Updated on June 19, 2013 12:04