Identification of a potent and nonpeptidyl CCR3 antagonist

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 [I-125]Eotaxin to CHO cells transfected with human CCR3 with an IC50 value of 2.3 nM. In human eosinophils, Compound X also inhibited Eotaxin-induced increases in intracellular Ca2+ 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. (C) 2001 Academic Press.