1. Academic Validation
  2. Characterization of YM-90709 as a novel antagonist which inhibits the binding of interleukin-5 to interleukin-5 receptor

Characterization of YM-90709 as a novel antagonist which inhibits the binding of interleukin-5 to interleukin-5 receptor

  • Int Immunopharmacol. 2002 Nov;2(12):1693-702. doi: 10.1016/s1567-5769(02)00191-1.
Tatsuaki Morokata 1 Kenji Ida Toshimitsu Yamada
Affiliations

Affiliation

  • 1 Inflammation Research Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.. 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. morokata@yamanouchi.co.jp
Abstract

Interleukin-5 (IL-5) plays an important role in the activation of eosinophils in allergic inflammation including asthma and atopic dermatitis. A newly synthesized compound, YM-90709, 2,3-dimethoxy-6,6-dimethyl-5,6-dihydrobenzo[7,8]indolizino [2,3-b]quinoxaline, is reported here to inhibit the binding of IL-5 to its receptor on peripheral human eosinophils and butyric acid-treated eosinophilic HL-60 clone 15 cells, with IC50 values of 1.0 and 0.57 microM, respectively. In contrast, YM-90709 did not affect the binding of granulocyte-macrophage colony-stimulating factor (GM-CSF) to its receptor on eosinophils and eosinophilic HL-60 clone 15 cells. In functional assays, YM-90709 inhibited IL-5-prolonged eosinophil survival with an IC50 value of 0.45 microM and did not affect the GM-CSF-prolonged eosinophil survival. Furthermore, YM-90709 inhibited the IL-5-induced but not GM-CSF-induced tyrosine phosphorylation of Janus kinase 2 (JAK2) in eosinophilic HL-60 clone 15 cells. These results indicate that YM-90709 is a novel IL-5 Inhibitor which selectively blocks the binding of IL-5 to the IL-5 Receptor (IL-5R).

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