Strategies for chemokine antagonists as therapeutics.
Chemokines are responsible for specific recruitment of leukocytes that are involved both in homing as well as in inflammation. Dysregulation of the system results in excessive recruitment to inflammatory sites and thus prevention of this recruitment is an effective anti-inflammatory strategy. Chemokine receptors are not limited only to cellular recruitment but are also the essential co-factor along with CD4 that enable HIV-1 viruses to infect cells. In this review we discuss the various points of intervention that can be addressed to provide anti-inflammatory and anti-HIV infectivity therapeutics. These include prevention of the receptor-ligand interaction, prevention of the chemokine-glycosaminoglycan interaction, interfering with the signaling pathways that are induced upon receptor activation, and modification of receptor trafficking pathways. We summarize the status of the approaches that have been undertaken to produce therapeutics that block chemokine action.
Proudfoot
Amanda E I
AE
Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan les Ouates, Geneva, Switzerland. amanda.proudfoot@serono.com
Power
Christine A
CA
Rommel
Christian
C
Wells
Timothy N C
TN
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D018925:Chemokines / Q000037:antagonists & inhibitors* / Q000276:immunology*; D015195:Drug Design; D006025:Glycosaminoglycans / Q000276:immunology / Q000378:metabolism; D006801:Humans; D021381:Protein Transport / Q000187:drug effects / Q000276:immunology; D011506:Proteins / Q000494:pharmacology; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D018925:Chemokines; D006025:Glycosaminoglycans; D011506:Proteins; D019707:Receptors, Chemokine