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Cell screening assay for identifying inhibitors of eosinophil proliferation
Author(s) -
KempeDustin Jessica J.,
AboulFadl Tarek,
Christensen Clarissa,
Palais Robert,
Parsawar Krishna,
Gleich Gerald J.,
Wagner Lori A.
Publication year - 2011
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20438
Subject(s) - eosinophil , lidocaine , asthma , pharmacology , cell growth , chemistry , cytokine , cell culture , immunology , medicine , biology , biochemistry , anesthesia , genetics
The purpose of this study was to develop a cell‐based screening assay for identification of small molecules for the treatment of asthma. Eosinophils are leukocytes that contribute to the pathology of asthma. Lidocaine inhibits interleukin‐5 (IL‐5)‐mediated survival and activation of human eosinophils, and it is able to replace inhaled glucocorticoids for the treatment of asthma; however, lidocaine has many side effects, including anesthesia. Therefore, a collection of commercial and novel, synthesized lidocaine analogues were investigated for inhibitory activity of the IL‐5‐stimulated proliferation of TF‐1 cells, a CD34 + , cytokine‐dependent, erythroleukemic cell line model for eosinophil growth. Among 74 investigated compounds, 10 were more potent inhibitors of cell proliferation than lidocaine (average IC 50 = 223 µM), with IC 50 values ranging within 1–119 µM. This cell‐based assay is an effective method for screening chemical compounds and has revealed promising lead compounds for the treatment of asthma. Drug Dev Res 72: 353–360, 2011. © 2011 Wiley‐Liss, Inc.