The Use of High-Content Screening for the Discovery and Characterization of Compounds That Modulate Mitotic Index and Cell Cycle Progression by Differing Mechanisms of Action
2006
The advent of high-content screening has expanded the ability of researchers to identify and quantify compound effects on a number of cellular events in a manner that allows for the rapid screening of chemical libraries. We have validated an approach for characterizing inhibitors of Aurora kinase family members using high-content screening by determining compound effects on the levels of the mitotic marker phospho-histone H3 (Ser10). Analysis of the data from these experiments led us to the discovery of a series of related compounds that increased the level of cells staining positive for the mitotic marker, indicating a block of cell cycle progression at M-phase. We then reconfigured the Aurora kinase inhibition assay and validated a high-content approach to identify compounds that block progression through M-phase. We were able to take advantage of the flexibility within the high-content screening platform to measure DNA content, activation of apoptosis, and effects on β-tubulin staining patterns, all of...
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
19
References
24
Citations
NaN
KQI