New chemical entities are desperately needed that overcome the limitations of existing drugs for neglected diseases. Screening a diverse library of 10,000 drug-like compounds against 7 neglected disease pathogens resulted in an integrated dataset of 744 hits. We discuss the prioritization of these hits for each pathogen and the strong correlation observed between compounds active against more than two pathogens and mammalian cell toxicity. Our work suggests that the efficiency of early drug discovery for neglected diseases can be enhanced through a collaborative, multi-pathogen approach.
The search for new drugs for human neglected diseases accelerated in the past decade, based on the recognition that addressing these infections was necessary for global poverty reduction. The expansion of discovery and development programmes was supported by donor investment, increasing participation of the industry and the creation of Product Development Partnership (PDP) enterprises. Despite these efforts, major discovery gaps remain as, apart from some repurposed drugs and a few new molecules for malaria, no new candidate has been recently transitioned from discovery into development for the major Neglected Tropical Diseases (NTDs). In this publication, we present a collaborative network model for drug discovery based on coordinated North-South partnerships. This network carried out low-to-medium throughput whole-organism screening assays against seven NTDs (malaria, leishmaniasis, human African trypanosomiasis [HAT], Chagas' disease, schistosomiasis, onchocerciasis and lymphatic filariasis) together with an early assessment of compound toxicity in mammalian cells. We describe a screening campaign of 10,000 molecules, its outcome and the implications of this strategy for enhancing the efficiency and productivity of drug discovery for NTDs.