PDE4NPD · Parasite-specific cyclic nucleotide phosphodiesterase inhibitors to target Neglected Parasitic Diseases

This project aims to unite global efforts to target the highly druggable class of enzymes called cyclic nucleotide phosphodiesterases (PDEs) in the fight for neglected parasitic diseases (NPD). It will establish a drug discovery platform, PDE4NPD, that combines phenotypic screening with efficient target-centric drug discovery, including target validation, various strategies for compound screening, PDE hit and lead optimization, safety and toxicology assessments and evaluation of anti-parasitic activity. The platform will make use of the target class expertise that the participating SMEs have gained when developing drugs for human and parasite PDEs, while all public partners offer proven experience in the field of NPD. The SMEs will adopt and progress existing PDE inhibitors that are in different stages of the drug discovery pipeline (i.e., target validation, hit and lead optimization). The current portfolio of inhibitors have clinical potential for treating sleeping sickness, Chagas' disease and leishmaniasis. Finding novel hits and leads for the PDEs that are associated with helminth diseases is also foreseen. The platform is open for targeting other NPD, and a broad panel of phenotypic screens (including malaria) is available to test PDE inhibitors. The phenotypic screening is performed by world-renowned groups, including two institutes in endemic countries. By capturing human and parasite PDE-related data in annotated chemogenomics databases, PDE-4-NPD will achieve the knowledge accumulation that is typical for target-centric approaches, thereby making the NPD drug development more efficient and enabling the SMEs to take advantage of the molecular understanding that is key for developing new medicines. The PDE4NPD platform constitutes an ideal basis for creating fruitful collaborations with both public and private partners word-wide.