| Small-molecule fluorophores to detect cell-state switching in the context of high-throughput screening. | |
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MedLine Citation:
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PMID: 18327938 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A small molecule capable of distinguishing the distinct states resulting from cellular differentiation would be of enormous value, for example, in efforts aimed at regenerative medicine. We screened a collection of fluorescent small molecules for the ability to distinguish the differentiated state of a mouse skeletal muscle cell line. High-throughput fluorescence-based screening of C2C12 myoblasts and myotubes resulted in the identification of six compounds with the desired selectivity, which was confirmed by high-content screening in the same cell states. The compound that resulted in the greatest fluorescence intensity difference between the cell states was used as the screening agent in a pilot screen of 84 kinase inhibitors, each present in four doses, for inhibition of myogenesis. Of the kinase inhibitors, 17 resulted in reduction of fluorescence at one or more concentrations; among the "hits" included known inhibitors of myogenesis, confirming that this compound is capable of detecting the differentiated myotube state. We suggest that the strategy of screening for screening agents reported here may be extended more broadly in the future. |
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Authors:
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Bridget K Wagner; Hyman A Carrinski; Young-Hoon Ahn; Yun Kyung Kim; Tamara J Gilbert; Dina A Fomina; Stuart L Schreiber; Young-Tae Chang; Paul A Clemons |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-03-08 |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: 130 ISSN: 1520-5126 ISO Abbreviation: J. Am. Chem. Soc. Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-03-26 Completed Date: 2008-04-25 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc Country: United States |
Other Details:
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Languages: eng Pagination: 4208-9 Citation Subset: IM |
Affiliation:
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Chemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA. bwagner@broad.harvard.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation / physiology* Cell Line Drug Evaluation, Preclinical Enzyme Activation / drug effects Enzyme Inhibitors / chemistry, metabolism, pharmacokinetics Fluorescent Dyes / chemistry*, metabolism, pharmacokinetics Mice Microscopy, Fluorescence Molecular Probes / chemistry*, metabolism, pharmacokinetics Molecular Weight Muscle Fibers, Skeletal / cytology, drug effects, metabolism* Myoblasts / cytology, drug effects, metabolism* Phosphotransferases / antagonists & inhibitors Predictive Value of Tests Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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DK060837/DK/NIDDK NIH HHS; P20-GM072029/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Fluorescent Dyes; 0/Molecular Probes; EC 2.7.-/Phosphotransferases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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