ReviewThe Journal of antimicrobial chemotherapy2026
A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 1: setting the stage.
Review in The Journal of antimicrobial chemotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Given the impact of kinetoplastid diseases, the limited therapeutic options and risk of treatment failure, continued research efforts to discover novel drug entities are required. The ambition to deliver drug development candidates has mainly been taken on board by academia and public private partnerships, but remains highly challenging because of the lack of adequate funding and standardized laboratory procedures. Establishing a systematic roadmap of experiments and decision criteria to attain high-quality leads and drug candidates with lower risk profiles remains the logical path to deliver more compelling proof-of-concepts for impactful diseases, such as African trypanosomiasis, Chagas disease and visceral and cutaneous leishmaniasis. In a three-part series, a structured roadmap from 'hit finding' to 'drug development candidate' is presented with a focus on the minimal essential data package, laboratory experimental models and endpoints. Part 1 introduces the concept of a pragmatic framework with reference to specific preclinical R&D stages: (i) hit finding, (ii) hit profiling, (iii) lead definition and (iv) drug development candidate to support a more focused early development path that remains accessible to engaged stakeholders. The experiment-oriented roadmap is presented in the next parts addressing the discovery and characterization of confirmed hits (Part 2) and the lead discovery phase towards identification of a drug development candidate (Part 3). Although specifically focusing on kinetoplastid diseases, the principles also apply to small-molecule preclinical R&D against other microbial diseases, evidently with specific adaptation of the primary pharmacology models.
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