Chemokine receptor antagonists: Part 1.
BACKGROUND
Chemokines were originally defined as host defense proteins, however, their biological role goes well beyond this simple description of their function as immune cell chemoattractants, and they have since been shown to be involved in a number of other biological processes, including growth regulation, hematopoiesis, embryologic development, angiogenesis, and HIV-1 infection. Because of their diverse role in autoimmune diseases and AIDS, chemokines and their receptors, which belong to the G-protein-coupled receptor superfamily, have been considered good drug targets by the pharmaceutical industry.


OBJECTIVE
In the first part of this two-part review, we highlight recent developments in the chemokine receptor antagonist field both in the peer reviewed and in the patent literature for the CC chemokine receptors CCR1, CCR2, CCR3, and CCR4.


CONCLUSIONS
A number of chemokine receptor antagonists have made the transition from lead compounds to clinical candidates, some of which are described here. Although there has been no clinical success yet for antagonists targeting the group of receptors discussed here, the compounds have been invaluable in generating information that should pave the way for producing successful therapeutics in the future.
Pease
James E
JE
Faculty of Medicine National Heart and Lung Institute, Imperial College of Science, Technology & Medicine, Leukocyte Biology Section, South Kensington Campus, London SW7 2AZ, UK. j.pease@imperial.ac.uk
Horuk
Richard
R
D000818:Animals; D019742:Chemokines, CC / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D010330:Patents as Topic; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors*; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors*; D054398:Receptors, CCR4 / Q000037:antagonists & inhibitors*
D019742:Chemokines, CC; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D054398:Receptors, CCR4