Authors

M Thomas²; I Gilbert²; T Miles¹; M De Rycker²; P Wyatt²; J M Fiandor-Roman¹; K D Read²;  ¹ GSK, Spain;  ² University of Dundee - Drug Discovery Unit, UK

Discussion

Visceral Leishmaniasis (VL) is a poverty associated parasitic infection responsible for around 40,000 deaths worldwide every year. Currently available treatments are hampered by issues such as toxicity, teratogenicity, cost and increasingly, resistance. There is therefore an urgent need for new treatments. The Drug Discovery Unit, University of Dundee, and the GlaxoSmithKline Kinetoplastid Discovery Performance Unit, Tres Cantos, with support from the Wellcome Trust, have formed a partnership to conduct drug discovery within kinetoplastid diseases, with a particular focus on VL. Within this collaboration, a novel chemical series was identified with in vitro activity in an intra-cellular Leishmania assay. This presentation will concentrate on the lead optimisation and progression of this series, focusing on the identification of compounds with in vivo efficacy, utilizing X-ray crystallography for optimization of solubility, and finally, progress towards candidate selection.