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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.<\/jats:p>\n                  <jats:p>In a three-part series, a structured roadmap from \u2018hit finding\u2019 to \u2018drug development candidate\u2019 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&amp;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).<\/jats:p>\n                  <jats:p>Although specifically focusing on kinetoplastid diseases, the principles also apply to small-molecule preclinical R&amp;D against other microbial diseases, evidently with specific adaptation of the primary pharmacology models.<\/jats:p>","DOI":"10.1093\/jac\/dkag109","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:47:13Z","timestamp":1774615633000},"source":"Crossref","is-referenced-by-count":0,"title":["A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 1: setting the stage"],"prefix":"10.1093","volume":"81","author":[{"given":"Sarah","family":"Hendrickx","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp , Wilrijk, Antwerp 2610 ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayhan","family":"Ilbeigi","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp , Wilrijk, Antwerp 2610 ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eli S J","family":"Thor\u00e9","sequence":"additional","affiliation":[{"name":"Department of Wildlife, Fish, and Environmental Studies, Swedish University of Agricultural Sciences , Ume\u00e5 907 36 ,","place":["Sweden"]},{"name":"Laboratory of Adaptive Biodynamics, Research Unit of Environmental and Evolutionary Biology, Institute of Life, Earth, and Environment, University of Namur , Namur 5000 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Universit\u00e9 Paris Cit\u00e9 , Paris 75006 ,","place":["France"]},{"name":"Centre de Recherche du CHU de Qu\u00e9bec, Universit\u00e9 Laval , Qu\u00e9bec, QC, G1V 4G2 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9bastien","family":"Pomel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CNRS BioCIS , 17 avenue des Sciences, Orsay 91400 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Alunda","sequence":"additional","affiliation":[{"name":"Department of Animal Health, Complutense University Madrid , Madrid 28040 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheraz","family":"Gul","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP , Discovery Research ScreeningPort, Hamburg 22525 ,","place":["Germany"]},{"name":"Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD , Hamburg 22525 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8583-5282","authenticated-orcid":false,"given":"Katrien","family":"Van Bocxlaer","sequence":"additional","affiliation":[{"name":"Skin Research Centre, Hull York Medical School, University of York , York YO10 5DD ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Fr\u00e9zard","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joana","family":"Tavares","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto , Porto 4200-135 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