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Mol Biosyst. 2006 Dec;2(12):609-20. Epub 2006 Oct 27.

Towards high-throughput characterization of small molecule mechanisms of action.

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Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA.


Drug discovery is hampered by the lack of general strategies to characterize the mechanisms of action and intracellular targets of bioactive small molecules. Genomics and proteomics promise to aid in this process. Genome-wide approaches in yeast have proven useful to infer the targets and target pathways of small molecules. These approaches are being systematically transferred into mammalian cell culture systems in order to interrogate more complex pathways in a more relevant setting. Advances in proteomics and in vivo genetic screening in multicellular model organism systems are also becoming increasingly powerful and amenable to high-throughput. Current methodologies and technologies are discussed, including how these global approaches complement affinity-based target identification strategies.

[Indexed for MEDLINE]

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