NDLI: A quantitative high-throughput screen for modulators of IL-6 signaling: a model for interrogating biological networks using chemical libraries

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A quantitative high-throughput screen for modulators of IL-6 signaling: a model for interrogating biological networks using chemical libraries

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Molecular BioSystems Vol - 5 Issue - 8

Molecular BioSystems Vol - 5 Issue - 7

Molecular BioSystems Vol - 5 Issue - 6

Molecular BioSystems Vol - 5 Issue - 5

Molecular BioSystems Vol - 5 Issue - 4

Molecular BioSystems Vol - 5 Issue - 3

Molecular BioSystems Vol - 5 Issue - 2

Molecular BioSystems Vol -4

Molecular BioSystems Vol -3

Molecular BioSystems Vol -2

A quantitative high-throughput screen for modulators of IL-6 signaling: a model for interrogating biological networks using chemical libraries

Content Provider	Royal Society of Chemistry (RSC)
Author	MacArthur, Ryan Wichterman, Jennifer Huang, Ruili Xia, Menghang Bi, Kun Southall, Noel Austin, Christopher P. Johnson, Ronald L. Printen, John Jadhav, Ajit Inglese, James
Copyright Year	2009
Abstract	Small molecule modulators are critical for dissecting and understanding signaling pathways at the molecular level. Interleukin 6 (IL-6) is a cytokine that signals via the JAK–STAT pathway and is implicated in cancer and inflammation. To identify modulators of this pathway, we screened a chemical collection against an IL-6 responsive cell line stably expressing a β-lactamase reporter gene fused to a sis-inducible element (SIE-bla cells). This assay was optimized for a 1536-well microplate format and screened against 11 693 small molecules using quantitative high-throughput screening (qHTS), a method that assays a chemical library at multiple concentrations to generate titration-response profiles for each compound. The qHTS recovered 564 actives with well-fit curves that clustered into 32 distinct chemical series of 13 activators and 19 inhibitors. A retrospective analysis of the qHTS data indicated that single concentration data at 1.5 and 7.7 μM scored 35 and 71% of qHTS actives, respectively, as inactive and were therefore false negatives. Following counter screens to identify fluorescent and non-selective series, we found four activator and one inhibitor series that modulated SIE-bla cells but did not show similar activity in reporter geneassays induced by EGF and hypoxia. Small molecules within these series will make useful tool compounds to investigate IL-6 signaling mediated by JAK–STAT activation.
Starting Page	1039
Ending Page	1050
Page Count	12
File Format	HTM / HTML PDF
ISSN	1742206X
Volume Number	5
Issue Number	9
Journal	Molecular BioSystems
DOI	10.1039/b902021g
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Beta-lactamase Microtiter plate EGF Cytokine High-throughput screening Enzyme inhibitor Tumor hypoxia Inflammation Interleukin 6 Reporter gene Gene Library Cancer
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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A Quantitative High-Throughput Screen for Modulators of IL-6 Signaling: A Model for Interrogating Biological Networks using Chemical Libraries

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A quantitative high-throughput screen for modulators of IL-6 signaling: a model for interrogating biological networks using chemical libraries

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