Current status of CCR1 antagonists in clinical trials

  • Ronald P. Gladue
  • Matthew F. Brown
Part of the Progress in Inflammation Research book series (PIR)


The chemokine receptor, CCR1, is believed to play a crucial role in the migration of leukocytes to sites of inflammation. It has been shown to be expressed on monocytes, T cells, dendritic cells, and in some cases, neutrophils [1, 2, 3, 4]) and interacts with at least 7 different ligands including CCL3 (MIP-1α, macrophage inflammatory protein-1α), CCL5 (RANTES, regulated on activation, normal T cell expressed and secreted), CCL7 (MCP-3, monocyte chemotactic protein-3), CCL14 (HCC-1, hemofiltrate C-C chemokine-1), CCL8 (MCP-2, monocyte chemotactic protein-2), CCL15 (leukotactin-1), and CCL23 (MPIF, myeloid progenitor inhibitory factor-1) [5, 6]. These ligands have been shown to have potent chemotactic activity in vitro [4] and, in some cases in vivo where intradermal injection of CCL3 or CCL5 induced a robust cellular infiltration [3, 7]. Further, these chemokines can be produced by the very cells they attract to inflammatory sites. For example, peripheral blood monocytes can secrete CCL3 following activation, potentially setting up an amplification loop whereby monocytes migrate into tissue in response to CCR1, then become activated and secrete CCR1 ligands such as CCL3, thereby recruiting more cells and setting up a state of chronic inflammation. These properties suggest that CCR1 may play an important role in perpetuating inflammatory responses.


Experimental Autoimmune Encephalomyelitis Chemokine Receptor Synovial Tissue Curr Opin Investig Drug Chemokine Receptor Antagonist 
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Copyright information

© Birkhäuser Verlag Basel/Switzerland 2007

Authors and Affiliations

  • Ronald P. Gladue
    • 1
  • Matthew F. Brown
    • 1
  1. 1.Department of Antibacterials, Immunology, and Cancer, MS 8220-2410Pfizer Global Research and DevelopmentGrotonUSA

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