TY - JOUR
T1 - Inhibitors of monocyte chemoattractant protein-1/CC ligand 2 and its receptor CCR2
AU - Howard, O. M.Z.
AU - Yoshimura, T.
N1 - Copyright:
Copyright 2005 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - 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 CCR2 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.
AB - 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 CCR2 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.
KW - Atherogenic disease
KW - CCL2
KW - CCR2
KW - Inflammation
KW - Monocyte chemoattractant proteins
KW - Tumour
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U2 - 10.1517/13543776.11.7.1147
DO - 10.1517/13543776.11.7.1147
M3 - Review article
AN - SCOPUS:0034944414
VL - 11
SP - 1147
EP - 1151
JO - Expert Opinion on Therapeutic Patents
JF - Expert Opinion on Therapeutic Patents
SN - 1354-3776
IS - 7
ER -