biostudies-literatureSmith ABill and Melinda Gates FoundationUK GovernmentWellcome Trust5606-5624https://www.ebi.ac.uk/biostudies/studies/S-EPMC9014415biostudies-literatureUnknown65(7)African animal trypanosomiasis or nagana, caused principally by infection of the protozoan parasites <i>Trypanosoma congolense</i> and <i>Trypanosoma vivax</i><i>,</i> is a major problem in cattle and other livestocks in sub-Saharan Africa. Current treatments are threatened by the emergence of drug resistance and there is an urgent need for new, effective drugs. Here, we report the repositioning of a compound series initially developed for the treatment of human African trypanosomiasis. A medicinal chemistry program, focused on deriving more soluble analogues, led to development of a lead compound capable of curing cattle infected with both <i>T. congolense</i> and <i>T. vivax</i> via intravenous dosing. Further optimization has the potential to yield a single-dose intramuscular treatment Journal of medicinal chemistryRepositioning of a Diaminothiazole Series Confirmed to Target the Cyclin-Dependent Kinase CRK12 for Use in the Treatment of African Animal Trypanosomiasis.PMC9014415218448218448/Z/19/Z105021105021/Z/14/Z202040100476OPP1093639103127Peter RRico Vidal EWall RJGillingwater KHampton SEMilne RNapier GVitouley HSDavis SHWitty MJGilbert IHWyllie SThomas MGDuke JHarrison JRRiley JRead KDBrun RSmith AHorn DCorpas Lopez VJeacock LBaker NHuggett MSimeons FRowan TZuccotto FPatterson SStojanovski LfalseRepositioning of a Diaminothiazole Series Confirmed to Target the Cyclin-Dependent Kinase CRK12 for Use in the Treatment of African Animal Trypanosomiasis.African animal trypanosomiasis or nagana, caused principally by infection of the protozoan parasites <i>Trypanosoma congolense</i> and <i>Trypanosoma vivax</i><i>,</i> is a major problem in cattle and other livestocks in sub-Saharan Africa. Current treatments are threatened by the emergence of drug resistance and there is an urgent need for new, effective drugs. Here, we report the repositioning of a compound series initially developed for the treatment of human African trypanosomiasis. A medicinal chemistry program, focused on deriving more soluble analogues, led to development of a lead compound capable of curing cattle infected with both <i>T. congolense</i> and <i>T. vivax</i> via intravenous dosing. Further optimization has the potential to yield a single-dose intramuscular treatment 2022-01-01T00:00:00Z2022 Apr2026-05-09T23:45:29.142Z2025-04-04T22:15:06.214ZS-EPMC90144153530341110.1021/acs.jmedchem.1c02104