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Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis
The binding of the tumor necrosis factor α (TNFα) to its cognate receptor initiates many immune and inflammatory processes. The drugs, etanercept (Enbrel(®)), infliximab (Remicade(®)), adalimumab (Humira(®)), certolizumab-pegol (Cimzia(®)), and golimumab (Simponi(®)), are anti-TNFα agents. These dru...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877629/ https://www.ncbi.nlm.nih.gov/pubmed/29518978 http://dx.doi.org/10.3390/ijms19030768 |
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author | Lim, Heejin Lee, Sang Hyung Lee, Hyun Tae Lee, Jee Un Son, Ji Young Shin, Woori Heo, Yong-Seok |
author_facet | Lim, Heejin Lee, Sang Hyung Lee, Hyun Tae Lee, Jee Un Son, Ji Young Shin, Woori Heo, Yong-Seok |
author_sort | Lim, Heejin |
collection | PubMed |
description | The binding of the tumor necrosis factor α (TNFα) to its cognate receptor initiates many immune and inflammatory processes. The drugs, etanercept (Enbrel(®)), infliximab (Remicade(®)), adalimumab (Humira(®)), certolizumab-pegol (Cimzia(®)), and golimumab (Simponi(®)), are anti-TNFα agents. These drugs block TNFα from interacting with its receptors and have enabled the development of breakthrough therapies for the treatment of several autoimmune inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, and psoriatic arthritis. In this review, we describe the latest works on the structural characterization of TNFα–TNFα antagonist interactions related to their therapeutic efficacy at the atomic level. A comprehensive comparison of the interactions of the TNFα blockers would provide a better understanding of the molecular mechanisms by which they neutralize TNFα. In addition, an enhanced understanding of the higher order complex structures and quinary structures of the TNFα antagonists can support the development of better biologics with the improved pharmacokinetic properties. Accumulation of these structural studies can provide a basis for the improvement of therapeutic agents against TNFα for the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases in which TNFα plays an important role in pathogenesis. |
format | Online Article Text |
id | pubmed-5877629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58776292018-04-09 Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis Lim, Heejin Lee, Sang Hyung Lee, Hyun Tae Lee, Jee Un Son, Ji Young Shin, Woori Heo, Yong-Seok Int J Mol Sci Review The binding of the tumor necrosis factor α (TNFα) to its cognate receptor initiates many immune and inflammatory processes. The drugs, etanercept (Enbrel(®)), infliximab (Remicade(®)), adalimumab (Humira(®)), certolizumab-pegol (Cimzia(®)), and golimumab (Simponi(®)), are anti-TNFα agents. These drugs block TNFα from interacting with its receptors and have enabled the development of breakthrough therapies for the treatment of several autoimmune inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, and psoriatic arthritis. In this review, we describe the latest works on the structural characterization of TNFα–TNFα antagonist interactions related to their therapeutic efficacy at the atomic level. A comprehensive comparison of the interactions of the TNFα blockers would provide a better understanding of the molecular mechanisms by which they neutralize TNFα. In addition, an enhanced understanding of the higher order complex structures and quinary structures of the TNFα antagonists can support the development of better biologics with the improved pharmacokinetic properties. Accumulation of these structural studies can provide a basis for the improvement of therapeutic agents against TNFα for the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases in which TNFα plays an important role in pathogenesis. MDPI 2018-03-07 /pmc/articles/PMC5877629/ /pubmed/29518978 http://dx.doi.org/10.3390/ijms19030768 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Lim, Heejin Lee, Sang Hyung Lee, Hyun Tae Lee, Jee Un Son, Ji Young Shin, Woori Heo, Yong-Seok Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis |
title | Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis |
title_full | Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis |
title_fullStr | Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis |
title_full_unstemmed | Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis |
title_short | Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis |
title_sort | structural biology of the tnfα antagonists used in the treatment of rheumatoid arthritis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877629/ https://www.ncbi.nlm.nih.gov/pubmed/29518978 http://dx.doi.org/10.3390/ijms19030768 |
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