CCR1 Antagonists: What Have We Learned From Clinical Trials

Author(s): Ronald P. Gladue, Matthew F. Brown, Samuel H. Zwillich.

Journal Name: Current Topics in Medicinal Chemistry

Volume 10 , Issue 13 , 2010

Submit Manuscript
Submit Proposal

Abstract:

The identification of chemokines and their receptors as potent mediators of leukocyte infiltration raised interest in the potential role of these proteins on disease pathogenesis. This is exemplified by the chemokine receptor, CCR1, which has been shown to be up-regulated in a number of human diseases, the implications of which have been suggested by animal models where inhibition of CCR1 or its ligands have shown beneficial effects. These data support the possibility that a CCR1 antagonist will provide therapeutic benefit to patients with inflammatory diseases. Over the last several years, several of these antagonists entered clinical trials, including CP-481,715 (Pfizer) and MLN3897 (Millennium) for rheumatoid arthritis, BX471 (Berlex / Scherring AG) for multiple sclerosis, and AZD-4818 (Astra-Zeneca) for COPD. This review will describe the evidence that supported the role of CCR1 in these diseases, the results from clinical trials, and provide perspectives on what has been learned from these trials for potential application / consideration to other studies with chemokine receptor antagonists.

Keywords: CCR1, CCL3, CCL5, Rheumatoid Arthritis, Multiple Sclerosis, CP-481, 715, BX471, MLN 3897, AZD-4818

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 10
ISSUE: 13
Year: 2010
Page: [1268 - 1277]
Pages: 10
DOI: 10.2174/156802610791561237
Price: $58

Article Metrics

PDF: 43