Projects per year
Abstract
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.
Original language | English |
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Pages (from-to) | 5606-5624 |
Number of pages | 19 |
Journal | Journal of Medicinal Chemistry |
Volume | 65 |
Issue number | 7 |
Early online date | 18 Mar 2022 |
DOIs | |
Publication status | Published - 14 Apr 2022 |
ASJC Scopus subject areas
- Drug Discovery
- Molecular Medicine
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A Platform for Drug Target Deconvolution and Exploitation
Gilbert, I. (Investigator), Horn, D. (Investigator), Pawlowic, M. C. (Investigator), Wyatt, P. (Investigator) & Wyllie, S. (Investigator)
31/12/20 → 30/05/25
Project: Research
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Chemical Biology: Leveraging Phenotypic Hits Against Kinetoplastids (Strategic Grant)
Fairlamb, A. (Investigator), Field, M. (Investigator), Gilbert, I. (Investigator), Gray, D. (Investigator), Horn, D. (Investigator) & Wyatt, P. (Investigator)
1/01/15 → 31/12/20
Project: Research
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New Treatment for African Animal Trypanosomiasis (Joint with GalvMed)
Gilbert, I. (Investigator), Hubbard, S. (Investigator) & Read, K. (Investigator)
Carnegie Trust for the Universities of Scotland
1/09/13 → 9/09/17
Project: Research