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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 structureDb06168
Related Articles
Protein chemical formulaC6452H9958N1722O2010S42
Protein average weight145200.0 Da
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
ACZ-885
ACZ885
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ilarisinjection, powder, lyophilized, for solution150 mg/mLsubcutaneousNovartis Pharmaceuticals Corporation2009-06-182016-04-23Us
Ilarispowder for solution150 mgsubcutaneousNovartis Pharmaceuticals Canada Inc2010-04-27Not applicableCanada
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII37CQ2C7X93
CAS number914613-48-2
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
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).
Related Articles
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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionsubcutaneous150 mg/mL
Powder for solutionsubcutaneous150 mg
PricesNot Available
PatentsNot Available
Properties
StateLiquid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General 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:19169963 ]
  2. 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. doi: 10.1056/NEJMoa0810787. [PubMed:19494217 ]
External Links
ATC CodesL04AC08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (120 KB)
MSDSDownload (568 KB)
Interactions
Drug Interactions
Drug
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Canakinumab.
AnakinraThe risk or severity of adverse effects can be increased when Anakinra is combined with Canakinumab.
BelimumabThe risk or severity of adverse effects can be increased when Canakinumab is combined with Belimumab.
Certolizumab pegolThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Canakinumab.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Canakinumab.
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Canakinumab.
golimumabThe risk or severity of adverse effects can be increased when golimumab is combined with Canakinumab.
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Canakinumab.
LeflunomideThe risk or severity of adverse effects can be increased when Canakinumab is combined with Leflunomide.
LenalidomideThe risk or severity of adverse effects can be increased when Lenalidomide is combined with Canakinumab.
NatalizumabThe risk or severity of adverse effects can be increased when Canakinumab is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Canakinumab.
PomalidomideThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Canakinumab.
RilonaceptThe risk or severity of adverse effects can be increased when Rilonacept is combined with Canakinumab.
RoflumilastRoflumilast may increase the immunosuppressive activities of Canakinumab.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Canakinumab.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Canakinumab.
ThalidomideThe risk or severity of adverse effects can be increased when Thalidomide is combined with Canakinumab.
TofacitinibCanakinumab may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Canakinumab.
Food Interactions
  • No food effects were found.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
binder
General Function:
Protein domain specific binding
Specific Function:
Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells.
Gene Name:
IL1B
Uniprot ID:
P01584
Molecular Weight:
30747.7 Da
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:19169963 ]
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Drug created on March 19, 2008 10:15 / Updated on March 14, 2016 10:03