Chemokine receptor antagonism as an approach to anti-inflammatory therapy: 'just right' or plain wrong?
Inflammation plays a pivotal role in exacerbating a wide array of human diseases. The chemokines are a group of proteins that control the movement and activation of the immune cells involved in all aspects of the inflammatory response. Recently, their cognate receptors have attracted considerable interest as therapeutic targets, in part because they are G-protein-coupled receptors, which have been antagonized successfully before by the pharmaceutical industry. Indeed, several companies have now reported the development of selective small-molecule chemokine receptor antagonists, and some of these compounds have even entered human Phase I clinical trials. Preclinical studies of the responsiveness of murine models of inflammation to either pharmacologic or genetic intervention have suggested that antagonism of some chemokine receptors may well prove to be a safe and efficacious approach to anti-inflammatory therapy.
Carter
Percy H
PH
Bristol-Myers Squibb Company, Experimental Station, Wilmington, DE 19880-0500, USA. percy.carter@bms.com
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D008024:Ligands; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D008024:Ligands; D019707:Receptors, Chemokine