AI Article Synopsis
- The activation and accumulation of leukocytes in inflamed tissues play a key role in developing inflammatory and autoimmune diseases like rheumatoid arthritis and multiple sclerosis.
- Research indicates that chemokines and their receptors, especially CCR1, are significant in this process and could serve as potential therapeutic targets.
- The review discusses the biology of CCR1, highlights its relevance in immune diseases, and outlines current drug discovery efforts focusing on CCR1 antagonists.
Article Abstract
The selective accumulation and activation of leukocytes in inflamed tissues contributes to the pathogenesis of inflammatory and autoimmune diseases such as infection, rheumatoid arthritis, allergic asthma, atopic dermatitis, and multiple sclerosis. A substantial body of reports suggests that chemokines and their receptors, which belong to a family of seven transmembrane G-protein coupled receptors (GPCR), may be involved in the selective accumulation and activation of leukocytes in inflamed tissues, and in the pathogenesis of inflammatory and autoimmune diseases. One such receptor is CCR1 which is a receptor for CC chemokines, such as CCL5 (RANTES) and CCL3 (MIP-1alpha). The involvement of CCR1 in immunological diseases now is documented in several preclinical studies with CCR1 deficient mice, anti-CCR1 antibodies and CCR1 antagonists, suggesting that CCR1 may be an attractive therapeutic target for a variety of diseases. Publications and patents describing CCR1 antagonists and their pharmacological effects have recently been disclosed. This review highlights the biology and pathophysiology of CCR1, and some of its currently reported antagonists. Additionally, our approach to CCR1 drug discovery is summarized.
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| http://dx.doi.org/10.2174/1381612033454937 | DOI Listing |
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