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Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview

The chemokine receptor 2 (CCR2) and chemokine receptor 5 (CCR5) are important mediators of leukocyte trafficking in inflammatory processes. The emerging evidence for a role of CCR2 and CCR5 receptors in human inflammatory diseases led to a growing interest in CCR2- and CCR5-selective antagonists. In...

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Autores principales: Junker, Anna, Kokornaczyk, Artur Kamil, Strunz, Ann Kathrin, Wünsch, Bernhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123309/
http://dx.doi.org/10.1007/7355_2014_40
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author Junker, Anna
Kokornaczyk, Artur Kamil
Strunz, Ann Kathrin
Wünsch, Bernhard
author_facet Junker, Anna
Kokornaczyk, Artur Kamil
Strunz, Ann Kathrin
Wünsch, Bernhard
author_sort Junker, Anna
collection PubMed
description The chemokine receptor 2 (CCR2) and chemokine receptor 5 (CCR5) are important mediators of leukocyte trafficking in inflammatory processes. The emerging evidence for a role of CCR2 and CCR5 receptors in human inflammatory diseases led to a growing interest in CCR2- and CCR5-selective antagonists. In this review, we focus on the recent development of selective CCR2/CCR5 receptor ligands and dual antagonists. Several compounds targeting CCR2, e.g., INCB8761 and MK0812, were developed as promising candidates for clinical trials, but failed to show clinical efficacy as presumed from preclinical models. The role of CCR5 receptors as the second co-receptor for the HIV-host cell fusion led to the development of various CCR5-selective ligands. Maraviroc is the first CCR5-targeting drug for the treatment of HIV-1 infections on the market. The role of CCR5 receptors in the progression of inflammatory processes fueled the use of CCR5 antagonists for the treatment of rheumatoid arthritis. Unfortunately, the use of maraviroc for the treatment of rheumatoid arthritis failed due to its inefficacy. Some of the ligands, e.g., TAK-779 and TAK-652, were also found to be dual antagonists of CCR2 and CCR5 receptors. The fact that CCR2 and CCR5 receptor antagonists contribute to the treatment of inflammatory diseases renders the development of dual antagonists as promising novel therapeutic strategy.
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spelling pubmed-71233092020-04-06 Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview Junker, Anna Kokornaczyk, Artur Kamil Strunz, Ann Kathrin Wünsch, Bernhard Chemokines Article The chemokine receptor 2 (CCR2) and chemokine receptor 5 (CCR5) are important mediators of leukocyte trafficking in inflammatory processes. The emerging evidence for a role of CCR2 and CCR5 receptors in human inflammatory diseases led to a growing interest in CCR2- and CCR5-selective antagonists. In this review, we focus on the recent development of selective CCR2/CCR5 receptor ligands and dual antagonists. Several compounds targeting CCR2, e.g., INCB8761 and MK0812, were developed as promising candidates for clinical trials, but failed to show clinical efficacy as presumed from preclinical models. The role of CCR5 receptors as the second co-receptor for the HIV-host cell fusion led to the development of various CCR5-selective ligands. Maraviroc is the first CCR5-targeting drug for the treatment of HIV-1 infections on the market. The role of CCR5 receptors in the progression of inflammatory processes fueled the use of CCR5 antagonists for the treatment of rheumatoid arthritis. Unfortunately, the use of maraviroc for the treatment of rheumatoid arthritis failed due to its inefficacy. Some of the ligands, e.g., TAK-779 and TAK-652, were also found to be dual antagonists of CCR2 and CCR5 receptors. The fact that CCR2 and CCR5 receptor antagonists contribute to the treatment of inflammatory diseases renders the development of dual antagonists as promising novel therapeutic strategy. 2014-03-05 /pmc/articles/PMC7123309/ http://dx.doi.org/10.1007/7355_2014_40 Text en © Springer-Verlag Berlin Heidelberg 2014 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Junker, Anna
Kokornaczyk, Artur Kamil
Strunz, Ann Kathrin
Wünsch, Bernhard
Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview
title Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview
title_full Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview
title_fullStr Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview
title_full_unstemmed Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview
title_short Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview
title_sort selective and dual targeting of ccr2 and ccr5 receptors: a current overview
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123309/
http://dx.doi.org/10.1007/7355_2014_40
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