Interfering with chemokine networks--the hope for new therapeutics.
Chemokines are a large family of cytokines with a wide variety of biological actions. Originally, they were identified as controllers of the routine trafficking of immune cells, and directed migration of cells during inflammatory response - from which they get their name, a contraction of chemotactic cytokines. They are now also known to be active in angiogenesis, embryonic development and infection by viruses such as HIV-1. Studies with antibodies, modified chemokine and transgenic mice suggest that chemokine receptor antagonists may be selective anti-inflammatory, antiviral or immunomodulatory agents. Small-molecule antagonists of seven of the receptors have been reported, some with potency in the low nanomolar range. These compounds are shown to be active in cell biology assays; the next step will be to determine their efficacy in animal models of disease.
Schwarz
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MK
Serono Pharmaceutical Research Institute, Ares-Serono International SA, 14 Chemin des Aux, 1228, Plan-Les-Ouates, Geneva, Switzerland.
Wells
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TN
D000818:Animals; D000906:Antibodies / Q000276:immunology; D018925:Chemokines / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D015335:Molecular Probes; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism / Q000502:physiology
D000906:Antibodies; D018925:Chemokines; D015335:Molecular Probes; D019707:Receptors, Chemokine