NPP-669

**NPP-669** is a novel, orally bioavailable prodrug of cidofovir (CDV) designed as a broad-spectrum antiviral therapeutic targeting double-stranded DNA (dsDNA) viruses. It features a C10 alkyl chain modification that enhances aqueous solubility, metabolic stability, cellular permeability, and rapid intracellular conversion to the active diphosphate metabolite (CDV-PP), achieving 2-3 orders of magnitude improved potency over CDV (e.g., EC50 <0.01 μM vs. ~1 μM for HCMV). In preclinical models, it demonstrated efficacy against cytomegalovirus (CMV) in mice (1 mg/kg BID p.o.) and adenovirus (AdV) in hamsters (0.1-3 mg/kg QD p.o., superior to brincidofovir in delayed treatment), with favorable pharmacokinetics (prolonged plasma/tissue CDV levels above EC50 for 24h), reduced kidney exposure, and no histological toxicity at 30 mg/kg QD.[1][2][3][4]