Theoretical analysis of efficacy of biological agent for rheumatoid arthritis based on target molecular binding occupancy
| العنوان: | Theoretical analysis of efficacy of biological agent for rheumatoid arthritis based on target molecular binding occupancy |
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| المؤلفون: | Haruko Yokoyama, Kanae Tani, Yasuhiko Yamada, Risa Takayanagi |
| المصدر: | Rheumatology International. 33:1791-1795 |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | musculoskeletal diseases, medicine.medical_specialty, Immunology, Molecular binding, Pharmacology, Antibodies, Monoclonal, Humanized, Models, Biological, Receptors, Tumor Necrosis Factor, Etanercept, Arthritis, Rheumatoid, Structure-Activity Relationship, chemistry.chemical_compound, Tocilizumab, Therapeutic index, Rheumatology, Internal medicine, Adalimumab, medicine, Animals, Humans, Immunology and Allergy, Drug Dosage Calculations, Molecular Targeted Therapy, Biological Products, Dose-Response Relationship, Drug, Molecular Structure, Tumor Necrosis Factor-alpha, business.industry, Antibodies, Monoclonal, medicine.disease, Receptors, Interleukin-6, Infliximab, chemistry, Antirheumatic Agents, Drug Design, Immunoglobulin G, Rheumatoid arthritis, business, Signal Transduction, medicine.drug |
| الوصف: | Recently, biological agents have been used for treatment of rheumatoid arthritis (RA), though the standard therapeutic doses vary among the agents utilized. To investigate the mechanisms related to those differences, we theoretically analyzed the target molecular binding occupancies of 4 biological agents: tocilizumab, infliximab, adalimumab, and etanercept. The average binding occupancy to the target molecule (Φss) was estimated to be 99.50 ± 0.44 % in a steady state after administration of the standard therapeutic dose of each agent. Furthermore, achieved American College of Rheumatology (ACR) 20, used as an index of clinical efficacy, increased in correlation with the value for Φss. These results suggest that clinical effects are achieved with a high value of target molecular binding occupancy. Thus, we considered that all of the agents examined in this study are antagonists and elicit clinical efficacy by inhibiting the signaling of biologically active substances that are not necessary for life maintenance and are secreted or released specifically in pathological conditions. In addition, target molecular binding occupancy can be used as an appropriate index for evaluating the standard therapeutic dose of biological agent for RA. |
| تدمد: | 1437-160X 0172-8172 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::87661bec83a6f4eb7931131bed858371 https://doi.org/10.1007/s00296-012-2650-7 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....87661bec83a6f4eb7931131bed858371 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 1437160X 01728172 |
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