Antimicrobial Agents and Chemotherapy · 2014 · 36 citations · 24 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryLead OptimizationDrug-target Interaction MappingEnzyme InhibitionHit-to-lead OptimizationLead DiscoveryAntitrypanosomal TherapyCombinatorial Lead GenerationDecarboxylase EnzymesProtein OverexpressionTherapeutic Target IdentificationTreatment Of TrypanosomiasisTrypanosoma Cruzi InfectionTrypanosome Infections
Elucidation of molecular targets is very important for lead optimization during the drug development process. We describe a direct method to find targets of antitrypanosomal compounds against Trypanosoma brucei using a trypanosome overexpression library. As proof of concept, we treated the library with difluoromethylornithine and DDD85646 and identified their respective targets, ornithine decarboxylase and N-myristoyltransferase. The overexpression library could be a useful tool to study the modes of action of novel antitrypanosomal drug candidates.
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Thousands of chemical starting points for antimalarial lead identification
Francisco‐Javier Gamo, Laura M. Sanz, Jaume Vidal et al. · Nature · 2010 · 1K citations
Chemical genetics of Plasmodium falciparum
W. Armand Guiguemde, Anang A. Shelat, David C. Bouck et al. · Nature · 2010 · 568 citations · Full text