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| Primary information |
|---|
| ID | 15008 |
| Therapeutic ID | Th1561 |
| Protein Name | Olokizumab |
| Sequence | NA
|
| Molecular Weight | NA |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | When administered either intravenously or subcutaneously to healthy volunteers, olokizumab has a half-life of 22.7-47.4 days.[A241195] |
| Description | 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.[A241185, A241175] Olokizumab is a humanized anti-IL-6 IgG4 antibody that directly blocks gp130 binding at IL-6 Site 3.[A241045] |
| Indication/Disease | NA |
| Pharmacodynamics | NA |
| Mechanism of Action | 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 TH17 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.[A241185, A241175] IL-6 signalling involves a corresponding IL-6 receptor (IL-6R/gp80/CD126) and a co-receptor gp130 (CD130).[A241185] 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.[A241175] 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.[A241185, A241175] Olokizumab is a humanized anti-IL-6 IgG4 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.[A241175] |
| Toxicity | NA |
| Metabolism | NA |
| Absorption | Olokizumab administered as a single escalating subcutaneous dose in healthy volunteers had a Cmax 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 AUC0-t and AUC0-8 ranges were 2,704 ± 886 to 24,723 ± 2,145 and 2,988 ± 1,124 to 30,444 ± 4,913 µg |
| When administered either intravenously or subcutaneously to healthy volunteers, olokizumab has a volume of distribution between 5.59-9.71 L.[A241195] |
| Clearance | When administered either intravenously or subcutaneously to healthy volunteers, olokizumab has a clearance of 0.116-0.204 L/day.[A241195] |
| Categories | Antibodies, Monoclonal, Humanized |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-6 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |