Development of IL-5 receptor antagonists.
A wealth of both clinical and pre-clinical data has strongly implicated the eosinophil in the pathogenesis of asthma, highlighting this cell type as a potential target for novel anti-inflammatory approaches to asthma therapy. The Th2 lymphocyte derived cytokine Interleukin-5 (IL-5) has emerged as the key regulator of eosinophil production, thus identifying IL-5 as the principal molecular target for therapeutic intervention. This review highlights both the pharmaceutical approaches, and the major challenges, to the identification of small molecule and protein antagonists of the IL-5 receptor. Using examples of known inhibitors we discuss their current status and highlight the major development hurdles in progressing these molecules into the market place.
Uings
Iain
I
Molecular Cell Biology Unit, GlaxoWellcome Research and Development, Stevenage, Herts., SG1 2NY, UK.
McKinnon
Murray
M
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019151:Peptide Library; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors* / Q000276:immunology; D053649:Receptors, Interleukin-5; D018418:Th2 Cells / Q000276:immunology
D018927:Anti-Asthmatic Agents; D019151:Peptide Library; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5