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Identification
Name Canakinumab
Accession Number DB06168
Type biotech
Groups approved
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). The biological activity of canakinumab is measured by comparing its inhibition of IL-1β-dependent expression of the reporter gene luciferase to that of a canakinumab internal reference standard, using a stably transfected cell line.
Protein structure No_structure_small
Protein chemical formula C6452H9958N1722O2010S42
Protein average weight 145200.0000
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

FASTA
Synonyms
ACZ-885
ACZ885
Salts Not Available
Brand names
Name Company
Ilaris Novartis
Brand mixtures Not Available
Categories Not Available
CAS number 914613-48-2
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication Investigated for use/treatment in rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory disorders (unspecified), and autoimmune diseases.
Pharmacodynamics Novartis AG is developing canakinumab, an intravenously or subcutaneously infused, 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) and possibly for other complex inflammatory diseases, such as rheumatoid arthritis, systemic-onset juvenile idiopathic arthritis (SoJIA), COPD disease and ocular diseases. Early 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.
Mechanism of action Canakinumab is a human monoclonal anti-human IL-1β antibody of the IgG1/κ isotype. Canakinumab binds to human IL-1β and neutralizes its activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1α or IL-1 receptor antagonist (IL-1ra).
Absorption The absolute bioavailability of subcutaneous canakinumab is estimated to be 70%.
Volume of distribution
  • 6.01 L [typical CAPS patient weighing 70 kg]
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life 26 days
Clearance
  • 0.174 L/day [typical CAPS patient weighing 70 kg]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers Not Available
Dosage forms
Form Route Strength
Injection, powder, for solution Subcutaneous 150mg/mL
Prices Not Available
Patents Not Available
Properties
State liquid
Experimental Properties Not Available
References
Synthesis Reference Not 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
External Links
Resource Link
Wikipedia http://en.wikipedia.org/wiki/Canakinumab Link_out
ATC Codes
  • L04AC08
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (120 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
Food Interactions Not Available
Targets

1. Interleukin-1 beta

Pharmacological action: unknown

Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells

Organism class: human
UniProt ID: P01584 Link_out
Gene: IL1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 November 27, 2010 15:15