CCR1 antagonists for the treatment of autoimmune diseases.
Chemokines are 8- to 10-kDa proteins that regulate leukocyte infiltration into inflammatory sites. The therapeutic potential of inhibiting these proteins is supported by their increased expression in human diseases, numerous studies in animal models of disease and, in some cases, by human genetic association studies. These findings, combined with the ability of chemokines to interact with 7-transmembrane G protein-coupled receptors, render them attractive drug discovery targets. This article reviews the evidence that supports a role for the chemokine receptor CCR1 in the pathogenesis of autoimmune diseases, progress made in identifying low molecular-weight antagonists and the current status of agents undergoing clinical evaluation.
Gladue
Ronald P
RP
Pfizer Global Research and Development, Department of Immunology, MS 8220-2410, Eastern Point Road, Groton, CT 06340, USA. ronald_p_gladue@Groton.Pfizer.com
Zwillich
Samuel H
SH
Clucas
Alan T
AT
Brown
Matthew F
MF
D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D015195:Drug Design; D006801:Humans; D008970:Molecular Weight; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
C515300:CCR1 protein, human; D054389:Receptors, CCR1; D019707:Receptors, Chemokine