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Journal of Biomolecular Screening, Vol. 8, No. 3, 324-331 (2003)
DOI: 10.1177/1087057103008003010
© 2003 Society for Biomolecular Sciences

Identification and Characterization of Novel Antagonists of the CCR3 Receptor

Usha Warrior

Usha.Warrior{at}abbott.com

Evelyn M. Mckeegan

Susan M. Rottinghaus

Lora Garcia

Linda Traphagen

George Grayson

Victoria Komater

Teresa McNally

Rosalind Helfrich

Richard R. Harris

Randy L. Bell

David J. Burns

Abbott Laboratories, Global Pharmaceutical Products Division, Abbott Park, IL.

Eotaxin, an inducer of eosinophil migration and activation, exerts its activity by binding to CCR3, the C-C chemokine receptor 3. An inhibitor of the eotaxin-CCR3 binding interaction may have potential as an anti-inflammatory drug for treatment of asthma, parasitic infections, and allergic disorders. A radioligand binding assay was developed using HEK cells transfected with CCR3, with 125I eotaxin as the ligand. Whole cells grown on polylysine-coated plates were used as the receptor source for the screen. Screening of more than 200,000 compounds with this assay yielded a number of screening hits, and of these, 2 active novel antagonists were identified. These compounds showed inhibitory effects on eosinophil chemotaxis in both in vitro and in vivo assays. (Journal of Biomolecular Screening 2003:324-331)

Key Words: eotaxin • CCR3 receptor • eosinophils • anti-inflammatory drugs • whole-cell receptor binding assays


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