PDE4NPD and the European Lead Factory team up: parasite enzyme up for ultra-HTS against 450,000 compounds

19 January 2017

With help of the European Lead Factory, the Phosphodiesterase Inhibitors for Neglected Parasitic Diseases (PDE4NPD) project takes the next step towards developing novel drugs against kinetoplastid parasites such as Trypanosoma brucei, the causative parasite of African sleeping sickness, and Trypanosoma cruzi, causing Chagas disease. Together, PDE4NPD and the EU Lead Factory will screen 450,000 compounds for their potential to inhibit one of the parasite PDEs the project has validated. 

Cyclic nucleotide phosphodiesterase (PDEs) are validated drug targets of many non-communicable diseases. There are also several proofs of their importance in the life cycle of many parasites causing devastating tropical diseases. Within the framework of the PDE4NPD project, an assay was developed that allows for high-throughput screening (HTS) of compounds against one of these parasite PDEs. With this assay, the PDE4NPD project could meet the technical requirements of the European Lead Factory and saw a chance to submit a proposal. Last week, the project received good news: the EU Lead Factory accepted the application. 

The EU Lead Factory Screening Selection Committee confirmed the high quality of the proposal: 'It’s an attractive approach with a well validated target. There is a high medical need, but finding selective inhibitors over human PDEs will be challenging.'

Prof Rob Leurs, Vrije Universiteit Amsterdam and PDE4NPD Principal Investigator commented 'Over the years, we’ve learnt which protein-ligand interactions provide specificity for the parasite PDEs. What we now need are scaffolds that will allow in vivo work. We are convinced that the high quality of the EU Lead Factory compound collection can provide that.'

On short notice, the PDE4NPD project, represented by the Vrije Universiteit Amsterdam, and the EU Lead Factory will form a programme team to ensure optimal planning, transfer and execution of the screen and hit selection.

Picture of Trypanosoma cruzi, one of the parasites targeted by PDE4NPD, courtesy of Fundação Oswaldo Cruz (Fiocruz).