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CCR1 antagonists

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Abstract

CCR1 (CC Chemokine receptor 1) is a widely studied G protein-coupled receptor target expressed on multiple types of leukocytes. It is implicated in initiating and exacerbating inflammatory conditions and thus is viewed as a good target for autoimmune and inflammatory therapeutic applications. Numerous CCR1 antagonists have been reported. Although some early CCR1 antagonists lacked the species cross reactivity that made in vivo animal model study difficult, efforts have been made to improve the compound potency in rodents. Recent identification of new and improved CCR1 antagonists has resulted in promising, in vivo efficacy in a variety of animal models of disease. While several early compounds have been withdrawn from clinical trials due to lack of efficacy, work continues to evaluate CCR1 antagonists in preclinical and clinical settings.

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Abbreviations

CCR1:

CC Chemokine receptor 1

CIA:

Collagen-induced arthritis

GPCR:

G protein-coupled receptor

HTS:

High-throughput screening

LPS:

Lipopolysaccharide

MCP:

Monocyte chemotactic proteins (MCP-1, −2, −3, −4, and −5)

MIP:

Macrophage inflammatory proteins (MIP-1α, MIP-1β)

RA:

Rheumatoid arthritis

RANTES:

Regulated upon Activation, Normal T Cell-expressed and Secreted

TID:

Ter in die, thrice-daily dosage

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  1. Tanabe Research Laboratories-USA, Inc., 4540 Towne Centre Court, San Diego, CA, 92121, USA

    Jie-Fei Cheng & Rick Jack

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  1. Jie-Fei Cheng
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Correspondence to Jie-Fei Cheng.

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Cheng, JF., Jack, R. CCR1 antagonists. Mol Divers 12, 17–23 (2008). https://doi.org/10.1007/s11030-008-9076-x

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