Abstract
Genomic-based methodologies are increasingly used at all stages of drug development. The most extensive applications have occurred in early drug discovery stages due to advances in technologies that allow for automated synthesis and characterization of organic compounds, and for high-throughput screening of these molecules against known drug targets. The adaptation of genomic-based methodologies in later stages of drug development presents a more difficult task.
In this review we describe how genomics can be used to identify previously uncharacterized pharmacologic actions that provide a basis for the development of new classes of antimycotic agents or for adverse event aversion. Clinically, novel antimycotics are gravely needed. This review provides a perspective on new technologies that will bridge the gap between drug discovery and development that may enable more rapid access to new antimycotic agents.
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Acknowledgments
The authors wish to thank Drs Alice Clark, XingCong Li, Hala ElSohly, Mohammed Ilias, Erdal Bedir, Ikhlas Khan, and their colleagues at the NCNPR; Drs Mark Hamann and Jordan Zjawiony, at the Department of Pharmacognosy, for their work in isolation of the antifungal actives; Drs Li and Zjawiony for preparation of analogs; Dr Chuck Dunbar (NCNPR) for structural elucidations; Drs Melissa Jacob and Shabana Khan of the NCNPR for most of the antifungal screening. All their hard work made evaluation and illustrations of many novel compounds possible.
This paper was funded by a grant from the National Institutes of Health (NIH grant no. AI49770-01A2) entitled, “Pharmacogenomics of natural products with antifungal activity”.
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Cleary, J.D., Walker, L.A. & Hawke, R.L. Antimycotic Drug Discovery in the Age of Genomics. Am J Pharmacogenomics 5, 365–386 (2005). https://doi.org/10.2165/00129785-200505060-00004
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DOI: https://doi.org/10.2165/00129785-200505060-00004