This study describes the development and evaluation of a new antimalarial drug candidate, NITD609, a spiroindolone. NITD609 is a fast-acting and potent schizonticidal drug against *Plasmodium falciparum* and *Plasmodium vivax* clinical isolates, with low nanomolar potency. It rapidly inhibits protein synthesis in *P. falciparum* and shows acceptable safety and pharmacokinetic properties, including the potential for once-daily oral dosing. In a rodent malaria model, NITD609 demonstrated single-dose efficacy. The study also identified mutations in the P-type cation-transporter ATPase4 (PfATP4) as the mechanism of drug resistance, with 11 non-synonymous mutations observed in resistant strains. These findings suggest that NITD609 has a novel mechanism of action and is a promising candidate for the treatment of malaria.This study describes the development and evaluation of a new antimalarial drug candidate, NITD609, a spiroindolone. NITD609 is a fast-acting and potent schizonticidal drug against *Plasmodium falciparum* and *Plasmodium vivax* clinical isolates, with low nanomolar potency. It rapidly inhibits protein synthesis in *P. falciparum* and shows acceptable safety and pharmacokinetic properties, including the potential for once-daily oral dosing. In a rodent malaria model, NITD609 demonstrated single-dose efficacy. The study also identified mutations in the P-type cation-transporter ATPase4 (PfATP4) as the mechanism of drug resistance, with 11 non-synonymous mutations observed in resistant strains. These findings suggest that NITD609 has a novel mechanism of action and is a promising candidate for the treatment of malaria.