A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 3: from lead towards a drug development candidate
Year: 2026
Type: review
Abstract: Neglected tropical diseases such as leishmaniasis, Chagas disease, sleeping sickness and animal trypanosomiasis remain a significant global health challenge. This part of the roadmap outlines a streamlined path for progressing from lead identification to a drug development candidate, tailored to the specific needs of kinetoplastid infections. Besides the medicinal upscaling of synthesis, this review highlights key experiments in pharmacology in non-rodent species, toxicology, pharmacokinetics and pharmaceutics. These include but are not limited to early evaluation of safety using refined in vitro and in vivo methods to enhance predictive value, bioavailability and distribution to target tissues, and formulation strategies leveraging various delivery systems to optimize efficacy and safety. Environmental toxicity is also addressed proactively, for which in silico tools are presented. Collectively, this roadmap provides a practical, scalable approach to deliver high-quality drug candidates capable of addressing the urgent needs for kinetoplastid diseases (Figure 1).
DOI: 10.1093/jac/dkag111
Authors: Sarah Hendrickx, Kayhan Ilbeigi, Eli S J Thoré, Michael G Bertram, Estefanía Calvo-Alvarez, Sener Cintesun, Ana Isabel Olías-Molero, María Jesús Corral, Marta Mateo-Barrientos, Jérôme Estaquier, Sébastien Pomel, José María Alunda, Sheraz Gul, Katrien Van Bocxlaer, Frédéric Frézard, Joana Tavares, Anabela Cordeiro Da Silva, Maria Paola Costi, Louis Maes, Guy Caljon
Institutions: University of Antwerp, University of Namur, Swedish University of Agricultural Sciences, Institute of Life, Earth and Environment, Stockholm University, Monash University, University of Milan, Yıldız Technical University, Universidad Complutense de Madrid, Inserm, Université Paris Cité, Health and Functional Exposomics, Université Laval, Centre de recherche du CHU de Québec-Université Laval, Centre National de la Recherche Scientifique, Université Paris-Saclay, Biomolécules : Conception, Isolement, Synthèse, Fraunhofer Institute for Translational Medicine and Pharmacology, Fraunhofer-Gesellschaft, University of York, Hull York Medical School, Universidade Federal de Minas Gerais, Universidade do Porto, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Instituto de Biologia Molecular e Celular, Instituto de Ciências Biomédicas Albel Salazar, University of Modena and Reggio Emilia
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,784
Awards: Scrutinizing the role of mast cells during human and murine Leishmania infections, Molecular basis for infection and quiescence of Leishmania in the bone marrow, G2657568419, G2777400950, G3239649357, G4304836912, G5867877676, Brain teaser: are impacts of pharmaceutical pollution on wildlife mediated by brain size?, G8217905538, G8721973322
OpenAlex ID: W7160841499