Funding: MRC, GCRF
Partners: GSK, Novartis, Ubiquigent, UbiQ
In recent years, drug discovery for leishmaniasis has focused on phenotypic screening approaches. Whilst several promising anti-leishmanial compounds have been identified and developed into pre-clinical candidates, complementary approaches are required to provide an alternative entry point for medicinal chemistry. Target-based drug discovery offers the opportunity to design potent and selective anti-parasitic compounds with a well-defined mechanism of action, which could provide safe, effective, affordable and convenient treatments to replace the inadequate treatment options for leishmaniasis. We are taking both genetic and chemical approaches to validate enzymes involved in post-translational modifications, with a focus on protein kinases, peptidases and epigenetic regulators. These are a promising group of enzymes for structure-based drug discovery for the following reasons. (a) Many enzymes involved in post-translational modifications are druggable (b) FDA approved drugs are in the market (c) Pharmaceutical companies have extensive experience of developing specific inhibitors against these target classes (d) Expertise can be used for anti-leishmanial drug discovery when appropriate targets and lead compounds have been identified.