Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview
| Autor: | Junker, Anna, Kokornaczyk, Artur Kamil, Strunz, Ann Kathrin, Wünsch, Bernhard |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
viruses
TAK-220 UK-107 543 UK-427 857 AZD5672 PF-4136309 Article Maraviroc PF-4254196 RANTES MK0483 parasitic diseases GSK163929 hERG INCB8761 RS504393 TAK-779 UK-347 503 MIP-1 MK0812 Chemokine receptors TAK-652 virus diseases PF-232798 SKB3380732 Atherosclerosis Inflammation JNJ17166864 INCB3284 INCB3344 HIV-1 INCB10820 CCR2 CCR5 MCP-1 |
| Zdroj: | Chemokines |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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