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 [(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.
Saeki
T
T
Tsukuba Research Institute, BANYU Pharmaceutical Co., Ltd., Okubo 3, Tsukuba, Ibaraki, 300-2611, Japan. saekith@banyu.co.jp
Ohwaki
K
K
Naya
A
A
Kobayashi
K
K
Ishikawa
M
M
Ohtake
N
N
Noguchi
K
K
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D006967:Hypersensitivity / Q000503:physiopathology; D051379:Mice; D011485:Protein Binding; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
C515350:CCR3 protein, human; C515351:Ccr3 protein, mouse; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D011994:Recombinant Proteins