AN3661

**AN3661** is a potent benzoxaborole antimalarial lead compound that targets **PfCPSF3**, the *Plasmodium falciparum* homologue of mammalian cleavage and polyadenylation specificity factor subunit 3, a pre-mRNA processing factor essential for mRNA maturation and stability. It exhibits low nanomolar activity (mean IC₅₀ ~32 nM) against multiple laboratory strains (e.g., 3D7, W2, Dd2) and Ugandan field isolates, with no cross-resistance to standard antimalarials, and demonstrates rapid parasiticidal effects particularly against trophozoite stages. AN3661 is orally bioavailable, achieving cure in mouse models of *P. berghei* (ED₉₀ 0.34 mg kg⁻¹) and *P. falciparum* (ED₉₀ 0.57 mg kg⁻¹) infections, with minimal mammalian cytotoxicity (CC₅₀ >60 μM). Resistance arises via mutations in the PfCPSF3 active site, where AN3661 binds by mimicking the transition state and phosphate, disrupting transcript stability for trophozoite-expressed genes.

Other names

benzoxaborole AN3661