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Tocilizumab

Cat. No. M6223
Tocilizumab Structure
Synonym:

MRA; atlizumab

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5mg USD 620  USD620 In stock
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Biological Activity

In vitro: Tocilizumab inhibits the binding of IL-6 to its receptors, and thus reduces the cytokines pro-inflammatory activity by competing for both the soluble and membrane-bound forms of the human IL-6 receptor. The inhibitory profile of anti-IL-6R mAb Tocilizumab is independent of membrane-bound IL-6R expression. Tocilizumab has anticancer potency via apoptosis induction as an agonistic IL-6R regulator. It has also been demonstrated that tocilizumab has an anti-proliferative effect on glioma cells via inhibition of the JAK-STAT3 pathway. Tocilizumab exhibits a significant growth inhibition in NSCLC cells (H460, A549, H1299 and H358), with proliferation significantly decreased by approximately 40% in A549 cells. Tocilizumab does not alter the levels of the ERK1/2, STAT3, NFκB and phosphorylated ERK1/2 and STAT3 proteins, but this antibody does considerably increase the expression of phosphorylated NFκB in NSCLC cells. Tocilizumab significantly inhibits expression of both IL-8 and MMP-9, known as the major angiogenic factors.

In vivo: A series of clinical studies has shown that inhibition of IL-6 signaling by tocilizumab is therapeutically effective in rheumatoid arthritis, juvenile idiopathic arthritis, Castleman's disease, and Crohn's disease. In all of these diseases, tocilizumab ameliorates inflammatory manifestations, and normalizes acute phase protein levels. Tocilizumab as a monotherapy and in combination, such as with methotrexate in case of rheumatoid arthritis, seems to be well tolerated. Tocilizumab markedly decreases the number of invaded capillary vessels in tumors.

Product Citations
Protocol (for reference only)
Cell Experiment
Cell lines non-small cell lung cancer (NSCLC) cells (A549, H460, H358 and H1299 cells)
Preparation method Ten microliters of tocilizumab, MTX or 5-FU are added to 96-well plates containing 104 cells per well in 100 µl medium. The final concentrations of tocilizumab are 10, 100 and 1000 ng/ml. The final concentrations of MTX and 5-FU are 50 and 25 µg/ml, respectively. Following a 24-h incubation, WST-1 solution is added, and the optical density is analyzed at reference wavelengths of 450 and 620 nm.
Concentrations 10, 100 and 1000 ng/ml
Incubation time 24 h
Animal Experiment
Animal models Male CB17/ICR-scid/scid mice (SCID mice)
Formulation PBS
Dosages 100 μg
Administration i.p.
Chemical Information
Molecular Weight 144984.63
Formula C6428H9976N1720O2018S42
CAS Number 375823-41-9
Storage -80°C for long term
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Ahmed A El-Zayadi, et al. Immunol Res. Anti-IL-6 receptor monoclonal antibody as a new treatment of endometriosis

[2] Xiao-Song Wu, et al. Int J Ophthalmol. Tocilizumab promotes corneal allograft survival in rats by modulating Treg-Th17 balance

[3] Aly M Abdelrahman, et al. Naunyn Schmiedebergs Arch Pharmacol. Effect of tocilizumab, an interleukin-6 inhibitor, on early stage streptozotocin-induced diabetic nephropathy in rats

[4] Yuangui Lin, et al. Eur J Pharmacol. Inhibition of interleukin-6 function attenuates the central sensitization and pain behavior induced by osteoarthritis

[5] Kim NH, et al. Oncol Lett. Anti-proliferative action of IL-6R-targeted antibody tocilizumab for non-small cell lung cancer cells.

[6] Peng Jiang, et al. Exp Ther Med. Intracisternal administration of an interleukin-6 receptor antagonist attenuates surgery-induced cognitive impairment by inhibition of neuroinflammatory responses in aged rats

[7] Hashizume M, et al. Int Rev Immunol. Tocilizumab, a humanized anti-IL-6R antibody, as an emerging therapeutic option for rheumatoid arthritis: molecular and cellular mechanistic insights.

[8] Esin Sogutlu Sari, et al. Curr Eye Res. Inhibitory effect of sub-conjunctival tocilizumab on alkali burn induced corneal neovascularization in rats

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Keywords: Tocilizumab, MRA; atlizumab supplier, IL Receptor/Related, inhibitors, activators


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