Inhibitors of monocyte chemoattractant protein-1/CC ligand 2 and its receptor CCR2

Chemoattractant cytokines (chemokines) have been shown to be pro-inflammatory and are thus likely targets for therapeutic intervention. An agent that interferes with directed migration of leukocytes to an inflammatory site is potentially a candidate anti-inflammatory drug. A specific chemokine, monocyte chemoattractant protein (MCP)-1 or CC ligand 2 (CCL2), and its receptor, CC-chemokine receptor 2 (CCR2), have been implicated in both acute and chronic inflammatory and autoimmune diseases associated with infiltration of monocytes, macrophages, dendritic cells, NK cells, basophils and memory T- cells. Genetic modification of CCL2 and CCRZ in murine models has demonstrated the potential for antagonists to prevent atherogenic vascular disease and autoimmune inflammatory diseases. Modified CCL2 peptides, which still bind but no longer activate CCR2, demonstrated the therapeutic potential of CCL2 inhibitors in animal models of arthritis. Several classes of small molecular weight CCL2 inhibitors have also been shown to inhibit chemotaxis in response to CCL2 in vitro and in animal models. However, more work is needed to establish the clinical efficacy of these CCL2 inhibitors.

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