CCR1 antagonists in clinical development.
Chemokines (chemotactic cytokines) are a family of low-molecular-weight proteins that direct the cellular migration of leukocytes by binding to and activating the G protein-coupled receptors displayed on the leukocyte cell surface. The inadvertent or excessive generation of chemokines has been associated with the inflammatory component of several disease processes, and consequently, considerable efforts have been made to characterise chemokine/chemokine receptor interactions with the ultimate aim of therapeutic intervention. This review focuses on the biology of CC chemokine receptor 1, which together with its ligands is thought to recruit leukocytes during the progression of rheumatoid arthritis, multiple sclerosis and organ transplant rejection. The developments made in antagonising this receptor and efficacies of these compounds in the clinical setting are also highlighted.
Pease
James E
JE
Biomedical Sciences Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, South Kensington Campus, London SW7 2AZ, UK. j.pease@imperial.ac.uk
Horuk
Richard
R
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000639:trends; D015507:Drugs, Investigational / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000639:trends*
C515300:CCR1 protein, human; D015507:Drugs, Investigational; D054389:Receptors, CCR1; D019707:Receptors, Chemokine