Chemokine blockers--therapeutics in the making?
Chemokines are a family of small chemoattractant cytokines that have an important role in controlling leukocyte migration. The finding that some chemokines and their receptors are upregulated in both acute and chronic inflammatory diseases, and that they are key players in the development of AIDS, has provided the pharmaceutical industry with new targets for therapeutic intervention in these diseases. Although the chemokine system shows apparent redundancy in vitro, target validation is possible largely through expression studies in human disease tissues and the use of transgenic and knockout mice as disease models. Several approaches are being developed to block the effects of chemokines, including small-molecule antagonists of chemokine receptors, modified chemokines and antibodies directed against chemokine receptors. Here, we describe the rationale behind these different approaches, the pitfalls that have been encountered and future perspectives.
Wells
Timothy N C
TN
Serono Pharmaceutical Research Institute, 1228 Plan-les-Ouates, Geneva, Switzerland. tim.wells@serono.com
Power
Christine A
CA
Shaw
Jeffrey P
JP
Proudfoot
Amanda E I
AE
D000818:Animals; D065100:CCR5 Receptor Antagonists; D018925:Chemokines / Q000037:antagonists & inhibitors*; D004804:Eosinophils / Q000502:physiology; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D011565:Psoriasis / Q000188:drug therapy; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction
C515350:CCR3 protein, human; D065100:CCR5 Receptor Antagonists; D018925:Chemokines; D006025:Glycosaminoglycans; D054397:Receptors, CCR3; D019707:Receptors, Chemokine