Repositioning of
a Diaminothiazole Series Confirmed
to Target the Cyclin-Dependent Kinase CRK12 for Use in the Treatment
of African Animal Trypanosomiasis
Posted on 2022-03-18 - 23:44
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.
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Smith, Alasdair; Wall, Richard J.; Patterson, Stephen; Rowan, Tim; Rico Vidal, Eva; Stojanovski, Laste; et al. (2022). Repositioning of
a Diaminothiazole Series Confirmed
to Target the Cyclin-Dependent Kinase CRK12 for Use in the Treatment
of African Animal Trypanosomiasis. ACS Publications. Collection. https://doi.org/10.1021/acs.jmedchem.1c02104