Journal Article

·2026 OPEN ACCESS

A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 2: from molecule to confirmed hit

Sarah Hendrickx , Kayhan Ilbeigi , Eli S. J. Thoré , Michael G. Bertram , Estefanía Calvo-Alvarez , Sener Cintesun YTU , Ana Isabel Olías-Molero , M. A. Corral , M. Mateo-Barrientos , Jérôme Estaquier ,

Journal of Antimicrobial Chemotherapy

Abstract

Given the medical importance and challenges related to kinetoplastid diseases, a strategic roadmap is needed for the identification of high-quality leads and drug development candidates. Within the aim to deliver more compelling proof-of-concept read-outs, this part proposes a systematic flow-chart of laboratory experiments and decision criteria, focusing on African trypanosomiasis, Chagas disease and visceral and cutaneous leishmaniasis. Next to precision experimental design and reporting, an overview is provided of various complementary laboratory models reproducing kinetoplastid infection and disease. Technical aspects of conventional in vitro and in vivo approaches and, more recently, in silico methods are presented with reference to specific preclinical R&D stages from 'hit finding' to 'profiling of a confirmed hit', covering the expertise areas of medicinal chemistry, primary pharmacology, (eco)toxicology, pharmacokinetics and pharmaceutics (Figure 1).

Keywords

Drug development Identification (biology) Drug discovery In silico Pharmaceutics Drug Computational biology Computer science

Subject Areas

Trypanosoma species research and implications ·Epidemiology ·Health Sciences
Research on Leishmaniasis Studies ·Public Health, Environmental and Occupational Health ·Health Sciences
Parasites and Host Interactions ·Parasitology ·Life Sciences

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