GS-621763

GS-621763 is an orally bioavailable prodrug form of the antiviral nucleotide analog GS-443902, which is also an active metabolite of remdesivir (Item No. 30354).^1,2 Upon intestinal absorption, GS-621763 is metabolized into the intermediate metabolite GS-441524 (Item No. 30469), which is then further metabolized to the active nucleotide triphosphate GS-443902 in cells where it induces RNA chain termination and inhibits viral polymerases.² It reduces the cytopathic effect of respiratory syncytial virus (RSV) in infected HEp-2 cells (EC₅₀ = 0.26 µM), as well as reduces viral titers in Vero E6 cells infected with various clinical isolates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; EC₅₀s = 0.11-0.73 µM). GS-621763 (10 mg/kg) inhibits viral transmission in ferrets infected with the SARS-CoV-2 variant of concern (VOC) P.1, also known as the gamma variant.²

WARNING This product is not for human or veterinary use.

1. Mackman, R.L., Hui, H.C., Perron, M., et al. Prodrugs of a 1'-CN-4-aza-7,9-dideazaadenosine C-nucleoside leading to the discovery of remdesivir (GS-5734) as a potent inhibitor of respiratory syncytial virus with efficacy in the african green monkey model of RSV. J. Med. Chem. 64(8), 5001-5017 (2021).

2. Cox, R.M., Wolf, J.D., Lieber, C.M., et al. Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferrets. Nat. Commun. 12(1), 6415 (2021).

Li, J., de Melo Jorge, D.M., Wang, W., et al. Differential bioactivation profiles of different GS-441524 prodrugs in cell and mouse models: ProTide prodrugs with high cell permeability and susceptibility to cathepsin a are more efficient in delivering antiviral active metabolites to the lung. J. Med. Chem. (2024).