Development of a Novel Compound Effective Against Juvenile, Adult, and Drug-Resistant Schistosoma Species

Schistosomiasis, a neglected tropical disease affecting over 250 million people worldwide, relies on praziquantel (PZQ) as its sole treatment. However, PZQ has significant limitations, including inactivity against juvenile worms, inability to prevent reinfection, and emerging drug resistance. In this review, we outline the development of CIDD-0150303, a novel oxamniquine (OXA) derivative with pan-species and pan-stage activity against Schistosoma mansoni, PZQ-resistant S. mansoni, and S. haematobium. Using a structure-guided design approach, over 350 OXA analogs were synthesized and screened to identify leading drug candidate CIDD-0150303. CIDD-0150303 demonstrates 100% lethality in vitro and up to 80% reduction in worm burden in vivo. CIDD-0150303 is effective against both juvenile and adult parasites as well as PZQ-resistant S. mansoni. This compound represents a promising advance in schistosomiasis treatment to address urgent gaps in control/elimination strategies and PZQ resistance. However, dedicated safety and toxicity studies are still ongoing, and additional in vivo validation is required.