02068nas a2200409   4500000000100000008004100001260001200042653001200054653002100066653002700087100001600114700001400130700001300144700001400157700002000171700001500191700002000206700001300226700002300239700001600262700001200278700001300290700001000303700001900313700001500332700001400347700001500361700001200376700001100388700001300399245016000412856007000572300001100642490000700653520098400660022001401644       2026                            d  c03/202610aRoadmap10adrug development10akinetoplastid diseases1 aHendrickx S1 aIlbeigi K1 aThoré E1 aBertram M1 aCalvo-Alvarez E1 aCintesun S1 aOlías-Molero A1 aCorral M1 aMateo-Barrientos M1 aEstaquier J1 aPomel S1 aAlunda J1 aGul S1 aVan Bocxlaer K1 aFrézard F1 aTavares J1 aDa Silva A1 aCosti M1 aMaes L1 aCaljon G00aA strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 2: from molecule to confirmed hit  uhttps://pmc.ncbi.nlm.nih.gov/articles/PMC13036319/pdf/dkag110.pdf  a1 - 140 v813 a<p>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).</p>  a1460-2091