The primary research focus of our lab is on discovery of new therapeutics for
neglected tropical diseases, using a "parachute" or "repurposing"
approach. In this approach, we identify parasitic targets of importance that have been
previously biochemically validated, with a further focus on those targets with human
homologs that have been pursued in human drug discovery. We then prepare known ligands
previously reported against the human homolog for assessment against the parasite target,
and then pursue an optimization program from that starting point. Our first project is
focused on trypanosomal phosphodiesterases, enzymes that have ~30% homology to human PDE4
and 5. Other projects focus on trypansomal TOR, Aurora kinases, dihydrofolate reductase,
and HDACs. Our secondary area of focus is on chemical technologies. Projects in this
category include diversification of lead compounds using reaction screening approaches,
applications of flow chemistry, and Green Chemistry. 

Articles

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Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 1. Sildenafil analogs (with Cuihua Wang, Trent D. Ashton, Alden Gustafson, Nicholas D. Bland, Stefan O. Ochiana, and Robert K. Campbell), Chemistry and Chemical Biology Faculty Publications (2012)

Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and...

 

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Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 2. Tadalafil analogs (with Stefan O. Ochiana, Alden Gustafson, Nicholas D. Bland, Cuihua Wang, Michael J. Russo, and Robert K. Campbell), Chemistry and Chemical Biology Faculty Publications (2012)

In this report we describe our ongoing target repurposing efforts focused on discovery of inhibitors...

 

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The susceptibility of trypanosomatid pathogens to PI3/mTOR kinase inhibitors affords a new opportunity for drug repurposing (with Rosario Diaz-Gonzalez, F. Matthew Kuhlmann, Cristina Galan-Rodriguez, Luciana Madeira da Silva, Caitlin E. Karver, Ana Rodriguez, Stephen M. Beverley, and Miguel Navarro), Chemistry and Chemical Biology Faculty Publications (2011)

Background

Target repurposing utilizes knowledge of "druggable" targets obtained in one organism and exploits this...

 

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Target repurposing for neglected diseases (with Robert K. Campbell), Chemistry and Chemical Biology Faculty Publications (2011)

Infectious diseases are an enormous burden to global health, and since drug discovery is costly,...

 

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The challenge of developing robust drugs to overcome resistance (with Celia Schiffer, Amy C. Anderson, and Norton P. Peet), Chemistry and Chemical Biology Faculty Publications (2011)

Drug resistance is problematic in microbial disease, viral disease and cancer. Understanding at the outset...