Projects per year
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.
|Number of pages||19|
|Journal||Journal of Medicinal Chemistry|
|Early online date||18 Mar 2022|
|Publication status||Published - 14 Apr 2022|
ASJC Scopus subject areas
- Drug Discovery
- Molecular Medicine
FingerprintDive into the research topics of 'Repositioning of a diaminothiazole series confirmed to target the cyclin-dependent kinase CRK12 for use in the treatment of African animal trypanosomiasis'. Together they form a unique fingerprint.
A Platform for Drug Target Deconvolution and Exploitation
Gilbert, I., Horn, D., Pawlowic, M., Wyatt, P. & Wyllie, S.
31/12/20 → 30/12/23
Chemical Biology: Leveraging Phenotypic Hits Against Kinetoplastids (Strategic Grant)
Fairlamb, A., Field, M., Gilbert, I., Gray, D., Horn, D. & Wyatt, P.
1/01/15 → 31/12/20
New Treatment for African Animal Trypanosomiasis (Joint with GalvMed)
Gilbert, I., Hubbard, S. & Read, K.
Wellcome Trust, Carnegie Trust for the Universities of Scotland
1/09/13 → 9/09/17