14 April 2016

PDE Toolbox plays a central role in parasite drug discovery and PDE biology

Last March, the PDE4NPD project submitted a very important deliverable: the PDE toolbox. The toolbox is a physical and virtual database with reference PDE inhibitors, DNA expression plasmids, and protocols. The project is currently halfway along, but already the PDE Toolbox is playing a central role both in parasite drug discovery and PDE biology. 

The objective of the PDE4NPD project is to produce a range of potent and selective parasite phosphodiesterase (PDE) inhibitors, and evaluate them as potential anti-parasitic drugs. To support tis objective, the PDE4NPD Project has assembled a “PDE Toolbox” containing a wide range of known and novel PDE inhibitors, which are profiled both biochemically (against purified PDE enzymes), and phenotypically (in cell-based assays) for their potential anti-parasitic effects.

Part of this toolbox comes from drug “repositioning” or “repurposing”, where pre-existing approved drugs targeting human PDEs can be immediately deployed against their parasite counterparts. In addition to acquiring commercially-available human PDEIs (hPDEIs), the Project also synthesizes specific compounds, using resources available at the partner’s facilities.

A wide range of other tools have also been assembled with which to carry out drug discovery operations. These include a wealth of DNA constructs with which to prime PDE expression in bacteria, human cells, parasites and baculovirus-infected insect cells. Also held within the Toolbox are the Protocols and Procedures for undertaking biochemical analyses.

Taken together, the components of the Toolbox provide a Discovery Matrix, through which to undertake the complex process of modern-day structure-based and phenotypic drug discovery. The Toolbox has played (and will continue to play) a central role in catalyzing anti-parasitic drug discovery within and beyond our Project. It is our long-term objective to integrate the results of our work with that of others in the NPD area, and we see the availability of tools and technologies such as the PDE Toolbox playing a key role in accelerating research in this area.