Fig. Examples of the diverse chemotypes that have been linked to PfATP4. Each of the compounds give rise to effects on the parasite's internal Na + concentration and pH that are consistent with PfATP4 inhibition . Since 2011, contributors to Open Source Malaria (OSM) have been evaluating several series of compounds originating from high-throughput screens (HTS) performed by pharmaceutical companies . The recent focus of OSM has been on a class of triazolopyrazine-based compounds ("Series 4") that emerged from a screen carried out at Pfizer. There are currently more than 200 compounds in Series 4, with in vitro potencies against P. falciparum ranging from single-digit nanomolar to inactive. The highly promising nature of this series derives from several members having been found to be effective in the in vivo mouse model of the disease . Based on preliminary investigations against PfATP4resistant mutant strains (generated from the parent Dd2 strain by exposure to hits from the Malaria Box against PfATP4 ), Series 4 compounds are thought to target PfATP4 . The intra-series similarity of their structures ought to imply a similarity in the way that the compounds interact with the target, but the interaction may differ from other compounds with the same phenotype.