Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks
Repositioning of a diaminothiazole series confirmed to target the cyclin-dependent kinase CRK12 for Use in the TREATMENT of African animal trypanosomiasis
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4651853
Author(s)
Smith, A.; Wall, R. J.; Patterson, S.; Rowan, T.; Rico Vidal, E.; Stojanovski, L.; Huggett, M.; Hampton, S. E.; Thomas, M. G.; Corpas Lopez, V.; Gillingwater, K.; Duke, J.; Napier, G.; Peter, R.; Vitouley, H. S.; Harrison, J. R.; Milne, R.; Jeacock, L.; Baker, N.; Davis, S. H.; Simeons, F.; Riley, J.; Horn, D.; Brun, R.; Zuccotto, F.; Witty, M. J.; Wyllie, S.; Read, K. D.; Gilbert, I. H.
Repositioning 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 Trypanosoma congolense and Trypanosoma vivax, 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 T. congolense and T. vivax via intravenous dosing. Further optimization has the potential to yield a single-dose intramuscular treatment for this disease. Comprehensive mode of action studies revealed that the molecular target of this promising compound and related analogues is the cyclin-dependent kinase CRK12.
