Identification of a potent and nonpeptidyl ccr3 antagonist.

Abstract CCR3 is expressed in a variety of leukocyte subsets, especially eosinophils, and may be involved in allergic disorders such as atopic asthma. To clarify the pathophysiological roles of CCR3 in allergic disorders, we developed a nonpeptidyl CCR3 antagonist. This antagonist, which is referred to as “Compound X,” that inhibited the binding of [ 125 I]Eotaxin to CHO cells transfected with human CCR3 with an IC 50 value of 2.3 nM. In human eosinophils, Compound X also inhibited Eotaxin-induced increases in intracellular Ca 2+ concentrations and chemotaxis. Thus, Compound X appears to be a highly potent CCR3 antagonist. These findings suggest that Compound X may be a useful tool for elucidating the pathophysiological roles of CCR3 in a variety of allergic disorders.