A decade of malaria phenotypic screenings: Key lessons on the discovery and development of new antimalarial drugs

Abstract Combating Malaria is still clearly required. According to last WHO report > 200 million cases of malaria and > 400,000 deaths were reported during 2017. Since 2010, emerging resistance to current front-line ACTs (Artemisinin Combination Therapies) has been detected in endemic countries. Therefore, there is an urgency for new therapies based on novel modes of action, which are able to relieve symptoms as fast as the artemisinins, as well as new therapies to block malaria transmission. A decade ago, the antimalarial community focused their efforts on phenotypic screenings as the most pragmatic approach to identify new antimalarial drugs able to cure blood stage clinical disease. Between 2008 and 2010 the results from 3 phenotypic HTS campaigns (GlaxoSmithKline, Novartis and St Jude's Children Hospital) comprising > 20,000 hits were reported and made publicly available. This data set represented an exciting and challenging opportunity for medicinal chemists on how to effectively triage in order to prioritize the most promising hits. In this paper we describe the different triage strategies we have followed at GSK as well as the outcomes and key learnings during the process.