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Drug Discovery Algorithm for Cutaneous Leishmaniasis

Max GroglDivision Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Drug Discovery Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemistry, University of Virginia, Charlottesville, Virginia

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Mark HickmanDivision Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Drug Discovery Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemistry, University of Virginia, Charlottesville, Virginia

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William EllisDivision Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Drug Discovery Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemistry, University of Virginia, Charlottesville, Virginia

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Thomas HudsonDivision Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Drug Discovery Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemistry, University of Virginia, Charlottesville, Virginia

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John S. LazoDivision Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Drug Discovery Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemistry, University of Virginia, Charlottesville, Virginia

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Elizabeth R. SharlowDivision Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Drug Discovery Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemistry, University of Virginia, Charlottesville, Virginia

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Jacob JohnsonDivision Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Drug Discovery Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemistry, University of Virginia, Charlottesville, Virginia

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Jonathan BermanDivision Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Drug Discovery Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemistry, University of Virginia, Charlottesville, Virginia

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Richard J. SciottiDivision Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Drug Discovery Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemistry, University of Virginia, Charlottesville, Virginia

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Cutaneous leishmaniasis is clinically widespread but lacks treatments that are effective and well tolerated. Because all present drugs have been grandfathered into clinical use, there are no examples of a pre-clinical product evaluation scheme that lead to new candidates for formal development. To provide oral agents for development targeting cutaneous leishmaniasis, we have implemented a discovery scheme that incorporates in vitro and in vivo testing of efficacy, toxicity, and pharmacokinetics/metabolism. Particular emphasis is placed on in vivo testing, progression from higher-throughput models to those with most clinical relevance, and efficient use of resources.

Author Notes

* Address correspondence to Richard J. Sciotti, Division Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910. E-mail: richard.sciotti@us.army.mil

Authors' addresses: Max Grogl, Mark Hickman, William Ellis, Thomas Hudson, Jacob Johnson, Jonathan Berman, and Richard J. Sciotti, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD, E-mails: max.grogl1@us.army.mil, mark.r.hickman@us.army.mil, bill.ellis@us.army.mil, thomas.hudson@us.army.mil, jjohnson@wrp-ksm.org, jbe9320457@aol.com, and richard.sciotti@us.army.mil. John S. Lazo, Department of Pharmacology and Chemistry, University of Virginia, Charlottesville, VA, E-mail: jsl8f@hscmail.mcc.virginia.edu. Elizabeth R. Sharlow, Department of Pharmacology, University of Virginia, Charlottesville, VA, E-mail: ers7g@virginia.edu.

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