Antagonists of CCR4 as immunomodulatory agents.
The chemokine receptor CCR4 is broadly expressed on cells of the immune system. It is known to play a central role in T cell migration to the thymus, and T cell maturation and education. In addition, CCR4 is known to modulate T cell migration to several sites of inflammation in the body, including the skin, and lungs. It is best known as a drug target for airway inflammation and atopic dermatitis, but cells expressing CCR4 are found in many inflammatory diseases. CCR4 small molecule antagonists have not yet reached the clinic, but at least one has been validated in an in vivo model. Here we review the current status of structurally novel CCR4 receptor antagonists.
Purandare
Ashok V
AV
Discovery Chemistry, Pharmaceutical Research Institute, Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ 08543-4000, USA. ashok.purandare@bms.com
Somerville
John E
JE
D000818:Animals; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D015195:Drug Design; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000276:immunology; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015394:Molecular Structure; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
C515354:CCR4 protein, human; D007155:Immunologic Factors; D054398:Receptors, CCR4; D019707:Receptors, Chemokine