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Small-molecule fluorophores to detect cell-state switching in the context of high-throughput screening
Journal article   Peer reviewed

Small-molecule fluorophores to detect cell-state switching in the context of high-throughput screening

Bridget K. Wagner, Hyman A. Carrinski, Young-Hoon Ahn, Yun Kyung Kim, Tamara J. Gilbert, Dina A. Fomina, Stuart L. Schreiber, Young-Tae Chang and Paul A. Clemons
Journal of the American Chemical Society, v 130(13), pp 4208-4209
02 Apr 2008
PMID: 18327938

Abstract

Chemistry Chemistry, Multidisciplinary Physical Sciences Science & Technology
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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Web of Science research areas
Chemistry, Multidisciplinary
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