Repurposing of the Open Access Malaria Box for Kinetoplastid Diseases Identifies Novel Active Scaffolds against Trypanosomatids.

摘要: Phenotypic screening had successfully been used for hit generation, especially in the field of neglected diseases, which feeding drug pipeline with new chemotypes remains a constant challenge. Here, we catalyze discovery research using publicly available tool to boost discovery. The Malaria Box, assembled by Medicines Venture, is structurally diverse set 200 druglike and probelike compounds distilled from more than 20,000 antimalarial hits corporate academic libraries. Repurposing such has already identified scaffolds against cryptosporidiosis schistosomiasis. In addition initiating hit-to-lead activities, Box plethora other parasites would enable community better understand similarities differences between them. We describe triaging kinetoplastids responsible human African trypanosomiasis (Trypanosoma brucei), Chagas disease cruzi), visceral leishmaniasis (Leishmania donovani Leishmania infantum). vitro vivo profiling most promising active respect efficacy, toxicity, pharmacokinetics, complementary druggable properties are presented collaborative model as way accelerate process discussed.