Conference Agenda

Parasitic worms continue to exert major health and economic burdens on humans and livestock, while escalating resistance to existing anthelmintics highlights the urgent need for novel chemotypes with distinct modes of action to support integrated control strategies. We screened 139,916 compounds from the Medicines for Malaria Venture Hit Generation Library 1 against exsheathed third-stage larvae of Haemonchus contortus, with cross-species assessment in Caenorhabditis elegans. High-throughput infrared-based motility and developmental assays in 384-well format showed robust performance (mean Z′ = 0.799 ± 0.012; signal-to-background = 65.6 ± 9.8). From this screen, 272 primary hits (0.194%) were identified, of which 110 reproducibly inhibited larval motility and development. Among these, 39 compounds exhibited IC₅₀ values <10 µM, and 33 induced complete developmental arrest at ≤12.5 µM, often with distinct morphological phenotypes. Four of the 39 compounds showed no detectable toxicity in HepG2 cells (CC₅₀ and MC₅₀ ≥20 µM), with ADME profiling available for a prioritsed subset. Integrating potency, selectivity and ADME properties enabled prioritisation of 16 compounds for advancement through medicinal chemistry. Collectively, these findings demonstrate that antimalarial-focused libraries can yield potent and selective nematocidal scaffolds, and highlight a scalable strategy for repurposing discovery libraries across various parasitic systems.