Abstract

Dr. Beatriz Baragana, Apicomplexan Portfolio Leader, Drug Discovery Unit (DDU), Wellcome Centre for Anti-infective Research (WCAIR), University of Dundee The Drug Discovery Unit (DDU) is a drug discovery engine that brings together assay development, screening, cell biology, medicinal chemistry, structural biology, computational chemistry and drug metabolism and pharmacokinetics (DMPK) in one integrated facility in the heart of the University of Dundee campus. We work in partnership with biopharma, product development partnerships (PDPs) and academic investigators to deliver high-quality preclinical packages for infectious diseases with a clear unmet medical need. Together with our pharma and product development partners, the DDU has delivered four candidate drugs currently in clinical development. Excitingly the first results of the clinical trials of a potential antimalarial compound discovered in the DDU have just been published by the QIMR Berghofer Medical Research Institute in Brisbane and Merck KGaA.1 The DDU malaria team, in partnership with Medicines for Malaria Venture, started with a hit molecule from a screen against the parasite which causes malaria and optimised this to deliver a compound, known as DDD107498 (M5717) as a preclinical candidate2. M5717 has the potential for single dose treatment of blood stage malaria, prevention of transmission and chemoprotection.3,4 It is very rare to find all these properties in one molecule. Further, M5717 works through a novel mechanism, which has not previously been found for malaria; the molecular target is the translation elongation factor eEF2. Merck KGaA took on the clinical development of this compound that is currently in Phase II trials. References 1.McCarthy, J. S. et. al, Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection study. Lancet Infect Dis 2021. 2.Hallyburton, I. et al, Screening a protein kinase inhibitor library against Plasmodium falciparum. Malar J 2017, 16, 446. 3.Baragana, B. et al, A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature 2015, 522, 315-320. 4.Baragana, B. et al, A novel multiple-stage antimalarial agent that inhibits protein synthesis (vol 522, pg 315, 2015). Nature 2016, 537, 122-122.