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DB06168 - Canakinumab


Identification
Name Canakinumab
Accession Number DB06168
Type biotech
Description Canakinumab is a recombinant, human anti-human-IL-1? monoclonal antibody that belongs to the IgG1/? 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-1? 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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 145200.0000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Used 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).
Mechanism of action In inflammatory diseases involving Cryopyrin-Associated Periodic Syndromes (CAPS), interleukin-1 beta (IL-1?) is excessively activated and drives inflammation. The protein cryopyrin controls the activation of IL-1?, and mutations in cryopyrin's gene, NLRP-3, up-regulate IL-1? activation. Canakinumab is a human monoclonal anti-human IL-1? antibody of the IgG1/? isotype. Canakinumab binds to human IL-1? and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1? or IL-1 receptor antagonist (IL-1ra).
Absorption The absolute bioavailability of subcutaneous canakinumab is estimated to be 70%.
Protein binding Canakinumab binds to plasma IL-1?, but plasma protein binding was not quantified.
Biotransformation The metabolism of canakinumab is not yet determined.
Route of elimination The route of elimination for canakinumab has not yet been determined.
Toxicity The 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
Interactions
Drug Interactions
Drug Mechanism of interaction
Adalimumab Increases immunosuppressive effects and risk of infection.
Alefacept Increases immunosuppressive effects and risk of infection.
Anakinra results in increased immunosuppressive effects; increases the risk of infection.
Antithymocyte globulin results in increased immunosuppressive effects; increases the risk of infection.
Azathioprine results in increased immunosuppressive effects; increases the risk of infection.
Basiliximab results in increased immunosuppressive effects; increases the risk of infection.
golimumab Avoid combination with canakinumab due to the increased chance of neutropenia and/or serious infection.
Natalizumab Avoid combination due to the increased risk of infection.
Pimecrolimus Avoid combination due the potential increase in immunosuppressant adverse effects.
Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
Tofacitinib Avoid combination with tofacitinib and other potent immunosuppressants due to potential enhancement of immunosuppressant effects.
Food Interactions
  • No food effects were found.

Targets


Interleukin-1 beta
Name Interleukin-1 beta
Gene Name IL1B
Pharmacological action yes
Actions binder
References
  • 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
DTHybrid score 1.0727

Predictions


Id Partner name Gene Name Score
5142 Protein-tyrosine-phosphatase PPI 0.084
6315 V-type proton ATPase subunit B, brain isoform ATP6V1B2 0.0737
4218 Ribonucleoside-diphosphate reductase M2 subunit RRM2 0.0692
566 Serotransferrin TF 0.062
798 Osteocalcin BGLAP 0.061
494 Caspase-1 CASP1 0.0296
1507 Cytochrome c CYCS 0.0269
22 30S ribosomal protein S4 rpsD 0.0266
6714 30S ribosomal protein S4 rpsD 0.0266
183 Vascular endothelial growth factor A VEGFA 0.0251
140 30S ribosomal protein S9 rpsI 0.0251
6719 30S ribosomal protein S9 rpsI 0.0251
6725 30S ribosomal protein S9 rpsI 0.0251
2077 Caspase-3 CASP3 0.0248
65 Matrix metalloproteinase-9 Not Available 0.0242
275 Arachidonate 5-lipoxygenase ALOX5 0.0213
1024 Solute carrier family 22 member 11 SLC22A11 0.0174
6143 Solute carrier family 22 member 7 SLC22A7 0.0172
6142 Solute carrier family 22 member 8 SLC22A8 0.0151
1729 Solute carrier family 22 member 6 SLC22A6 0.0138
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