DT-Web

DB06273 - Tocilizumab


Identification
Name Tocilizumab
Accession Number DB06273
Type biotech
Description Tocilizumab is a recombinant, humanized, anti-human interleukin 6 (IL-6) receptor monoclonal antibody that achieves a significant therapeutic response rate. The light chain is made up of 214 amino acids. The heavy chain is made up of 448 amino acids. The four polypeptide chains are linked intra- and inter-molecularly by disulfide bonds. FDA approved on January 8, 2010.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 148 kDa
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs). It is also indicated for the treatment of active polyarticular juvenile idiopathic arthritis (PJIA) and active systemic juvenile idiopathic arthritis (SJIA) in patients 2 years of age and older.
Mechanism of action Interleukin (IL)-6 plays essential roles not only in the immune response, but also in haematopoiesis and the central nervous system. Deregulated production of IL-6 has been found in chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA), systemic onset juvenile idiopathic arthritis (soJIA), Crohn's disease (CD) and systemic lupus erythematosus (SLE). Furthermore, IL-6 activities can explain many symptoms of these diseases. More importantly, serum levels of IL-6 are correlated with disease activity. Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors.
Absorption When 4 mg/kg of tocilizumab was given every 4 weeks to RA patients, the pharmacokinetic parameters at steady state are as follows: AUC = 13000 ? 5800 mcg?h/mL; Cmax = 88.3 ? 41.4 mcg/mL. Tocilizumab accumulates following repeated doses. Furthermore, an increased body weight may increase plasma levels of tocilizumab. When a dose of 8 mg/kg of tocilizumab is given to PJIA patients, the pharmacokinetic parameters are as follows: AUC = 29500 ? 8660 mcg?h/mL; Cmax = 182 ? 37 mcg/mL. When a dose of 8 mg/kg of tocilizumab is given to SJIA patients, the pharmacokinetic parameters are as follows: AUC = 32200 ? 9960 mcg?h/mL; Cmax = 245 ? 57.2 mcg/mL.
Protein binding Not Available
Biotransformation Not Available
Route of elimination Following intravenous dosing, tocilizumab undergoes biphasic elimination from the circulation.
Toxicity Most common adverse reactions (incidence of at least 5%): upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Dextromethorphan Dextromethorphan is a CYP2D6 and CYP3A4 substrate. Exposure of dextromethorphan decreases following administration of tocilizumab.
golimumab Avoid combination due to the enhanced immunosuppression by TNF blockers.
Omeprazole Omeprazole is a CYP2C19 and CYP3A4 substrate. Exposure of omeprazole decreases following administration of tocilizumab..
Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
Simvastatin Simvastatin is a CYP3A4 and OATP1B1 substrate. Exposure of simvastatin decreases following administration of tocilizumab.
Tofacitinib Avoid combination due to the potential increase in tofacitinib related adverse effects.
Food Interactions Not Available

Targets


Interleukin-6 receptor alpha chain
Name Interleukin-6 receptor alpha chain
Gene Name IL6R
Pharmacological action yes
Actions antibody
References
  • Smolen JS, Maini RN: Interleukin-6: a new therapeutic target. Arthritis Res Ther. 2006;8 Suppl 2:S5. Epub 2006 Jul 28. - Pubmed
DTHybrid score 1.0152

Predictions


Id Partner name Gene Name Score
4878 Glycoprotein hormones alpha chain CGA 0.0148
1052 Cytotoxic T-lymphocyte protein 4 CTLA4 0.0148
1072 Granzyme B GZMB 0.0148
4850 Beta-2-glycoprotein 1 APOH 0.0148
4880 Membrane cofactor protein CD46 0.0148
1563 Platelet glycoprotein Ib alpha chain GP1BA 0.0148
442 Envelope glycoprotein gp41 0.0148
4859 Envelope glycoprotein env 0.0148
4889 Ig epsilon chain C region IGHE 0.0148
4189 Alpha-galactosidase A GLA 0.0148
4869 Major capsid protein A430L 0.0148
4852 Reticulon-4 receptor RTN4R 0.0148
4877 Beta-mannanase man 0.0148
4856 CD209 antigen CD209 0.0148
4845 ADAM 33 ADAM33 0.0148
757 Fusion glycoprotein F0 F 0.0148
4875 Fusion glycoprotein F0 F 0.0148
4871 Endo-beta-N-acetylglucosaminidase F3 endOF3 0.0148
1354 Beta-glucuronidase GUSB 0.0148
4882 Dipeptidyl aminopeptidase-like protein 6 DPP6 0.0148
4721 Beta-1,4-mannanase manA 0.0148
3352 Structural polyprotein Not Available 0.0148
3628 Structural polyprotein Not Available 0.0148
4892 Structural polyprotein Not Available 0.0148
1184 Interferon beta IFNB1 0.0129
6858 Inactive carboxylesterase 4 CES1P1 0.0129
1379 Interleukin-12 subunit beta IL12B 0.0129
4193 Atrial natriuretic peptide clearance receptor NPR3 0.0129
793 T-cell surface antigen CD2 CD2 0.0129
119 Carcinoembryonic antigen-related cell adhesion molecule 1 CEACAM1 0.0129
4857 Zinc-alpha-2-glycoprotein AZGP1 0.0129
4890 Hemagglutinin HA 0.0129
6566 Hemagglutinin Not Available 0.0129
3837 Cytokine receptor common beta chain CSF2RB 0.0129
554 Low-density lipoprotein receptor LDLR 0.0129
3444 Cyanovirin-N Not Available 0.0119
18 High affinity immunoglobulin epsilon receptor subunit alpha FCER1A 0.0119
1859 Prostatic acid phosphatase ACPP 0.0119
2998 Sialic acid-binding Ig-like lectin 7 SIGLEC7 0.0119
852 Heparin cofactor 2 SERPIND1 0.0119
3258 Mannosyl-oligosaccharide alpha-1,2-mannosidase MSDC 0.0119
3140 Hemagglutinin-neuraminidase HN 0.0119
3609 Hemagglutinin-neuraminidase HN 0.0119
2297 Genome polyprotein Not Available 0.0119
2322 Genome polyprotein Not Available 0.0119
2694 Genome polyprotein Not Available 0.0119
2719 Genome polyprotein Not Available 0.0119
2860 Genome polyprotein Not Available 0.0119
2928 Genome polyprotein Not Available 0.0119
3160 Genome polyprotein Not Available 0.0119
3260 Genome polyprotein Not Available 0.0119
4783 Genome polyprotein Not Available 0.0119
5726 Genome polyprotein Not Available 0.0119
5779 Genome polyprotein Not Available 0.0119
5867 Genome polyprotein Not Available 0.0119
6253 Genome polyprotein Not Available 0.0119
6301 Genome polyprotein Not Available 0.0119
6380 Genome polyprotein Not Available 0.0119
6381 Genome polyprotein Not Available 0.0119
6437 Genome polyprotein Not Available 0.0119
6520 Genome polyprotein Not Available 0.0119
6521 Genome polyprotein Not Available 0.0119
6652 Genome polyprotein Not Available 0.0119
6734 Genome polyprotein Not Available 0.0119
6735 Genome polyprotein Not Available 0.0119
6736 Genome polyprotein Not Available 0.0119
6737 Genome polyprotein Not Available 0.0119
6738 Genome polyprotein Not Available 0.0119
6739 Genome polyprotein Not Available 0.0119
6744 Genome polyprotein Not Available 0.0119
6748 Genome polyprotein Not Available 0.0119
6894 Genome polyprotein Not Available 0.0119
6898 Genome polyprotein Not Available 0.0119
6120 Cation-independent mannose-6-phosphate receptor IGF2R 0.0119
4666 Fucose-binding lectin PA-IIL lecB 0.0112
2372 Bifunctional tail protein 9 0.0112
4787 Envelope glycoprotein gp160 env 0.0112
4820 Envelope glycoprotein gp160 env 0.0112
5727 Envelope glycoprotein gp160 env 0.0112
2577 Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase MAN1B1 0.0107
3480 Mannan endo-1,4-beta-mannosidase manA 0.0104
64 Neuraminidase NA 0.0104
641 Neuraminidase NA 0.0104
2676 Neuraminidase NA 0.0104
3026 Neuraminidase NA 0.0104
3519 Neuraminidase NA 0.0104
6007 Neuraminidase NA 0.0104
595 Fibrinogen alpha chain FGA 0.0103
1782 Neutrophil gelatinase-associated lipocalin LCN2 0.01
1439 Lactotransferrin LTF 0.01
1243 Cathepsin D CTSD 0.0098
2430 Chondroitinase B cslB 0.0095
958 Insulin-like growth factor 1 receptor IGF1R 0.0095
6307 Ig gamma-2 chain C region IGHG2 0.0094
309 Antithrombin-III SERPINC1 0.0093
2581 Chondroitinase AC cslA 0.0093
6847 Lactase-phlorizin hydrolase LCT 0.0093
6500 Phospholipase A2 PLA2G1B 0.009
2207 Rhodopsin RHO 0.0087
3814 Complement C1r subcomponent C1R 0.0082
4785 Ig gamma-1 chain C region IGHG1 0.0078
4604 Liver carboxylesterase 1 CES1 0.0078
76 Nitric-oxide synthase, brain NOS1 0.0077
952 Dipeptidyl peptidase 4 DPP4 0.0067
3923 Cholinesterase BCHE 0.0064
20 Prostaglandin G/H synthase 1 PTGS1 0.0059
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