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Olokizumab API Manufacturers & Suppliers

General Description:

Olokizumab, identified by CAS number 1007223-17-7, is a notable compound with significant therapeutic applications. Interleukin-6 (IL-6) is an important cytokine with roles in immune cell proliferation/differentiation, energy and bone metabolism, and the acute phase response of the innate immune system. IL-6 pathway dysregulation is associated with chronic inflammation and lymphoproliferation, including in autoimmune conditions such as rheumatoid arthritis, Castleman disease, and cytokine release syndrome. Targeting IL-6 function can be achieved directly, or through interrupting the IL-6 receptor or gp130 receptor axes. Olokizumab is a humanized anti-IL-6 IgG4κ antibody that directly blocks gp130 binding at IL-6 Site 3.

Absorption:

The absorption characteristics of Olokizumab are crucial for its therapeutic efficacy: Olokizumab administered as a single escalating subcutaneous dose in healthy volunteers had a C_max between 2.99 ± 0.271 and 22.3 ± 4.48 μg/mL for doses between 0.3 and 3.0 mg/kg. The maximum concentration was achieved at a median of between 120 and 336 hours. The corresponding AUC_0-t and AUC_0-∞ ranges were 2,704 ± 886 to 24,723 ± 2,145 and 2,988 ± 1,124 to 30,444 ± 4,913 μg\*h/mL, respectively. The bioavailability ranged between 85.7-92.5%. When administered as a single escalating intravenous dose between 0.001-10.0 mg/kg, the C_max varied between 0.242 ± 0.0262 and 207 ± 14.7 μg/mL and was typically achieved within a median time of 2-4 hours. The corresponding AUC_0-t and AUC_0-∞ ranges were 101 ± 46.3 to 120,294 ± 16,882 and 303 ± 111 to 159,072 ± 50,801 μg\*h/mL, respectively. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Olokizumab is an important consideration for its dosing schedule: When administered either intravenously or subcutaneously to healthy volunteers, olokizumab has a half-life of 22.7-47.4 days. This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Olokizumab is distributed throughout the body with a volume of distribution of: When administered either intravenously or subcutaneously to healthy volunteers, olokizumab has a volume of distribution between 5.59-9.71 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Olokizumab is a critical factor in determining its safe and effective dosage: When administered either intravenously or subcutaneously to healthy volunteers, olokizumab has a clearance of 0.116-0.204 L/day. It reflects the efficiency with which the drug is removed from the systemic circulation.

Mechanism of Action:

Olokizumab functions by: Interleukin-6 (IL-6) plays a role in numerous autoimmune diseases by perpetuating tissue damage and inflammation. IL-6 acts as an essential differentiation factor for T_H17 cells, which, when activated through dendritic cells displaying antigen-specific signals, induce tissue damage and act pathogenically. IL-6 also functions in B cell differentiation and development, including in the production of pathogenic autoantibodies. Combined with other roles for IL-6 in cell proliferation and differentiation, these mechanisms underly the importance of IL-6 in a variety of autoimmune conditions. IL-6 signalling involves a corresponding IL-6 receptor (IL-6R/gp80/CD126) and a co-receptor gp130 (CD130). Complex assembly is thought to involve binding of IL-6 to gp80 at Site 1 followed by binding to gp130 at Site 2 to form a heterotrimer; two heterotrimers then combine through Site 3 on IL-6 binding to domain 1 of gp130. The resulting heterohexameric complex is responsible for signal transduction. Curiously, although IL-6R is typically membrane-bound, it can also exist in a soluble form (sIL-6R) through limited proteolysis or alternative splicing. This leads to three distinct signalling paradigms: classic signalling, where IL-6R and gp130 exist within the same cell membrane, _trans_-signalling, where sIL-6R interacts with membrane-bound gp130, and _trans_-presentation, where IL-6R from one cell forms a complex with gp130 on a different cell. It is thought that _trans_-signalling is responsible for the majority of IL-6-associated pathology. Olokizumab is a humanized anti-IL-6 IgG4κ antibody whose epitope lies within IL-6 Site 3. Structural analysis revealed that olokizumab binding induces conformational changes in IL-6 that cause occlusion of the gp130 binding site between trp157 and residues 50-60. By inhibiting gp130 binding, olokizumab inhibits both classical and _trans_-signalling. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Classification:

Olokizumab belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Olokizumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Blood Proteins, Globulins, Immunoglobulins, Immunoproteins, Proteins, Serum Globulins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.