Rovafovir etalafenamide

Rovafovir etalafenamide (GS-9131), a proagent of the adenosine nucleotide analogue GS-9148, is an orally active nucleoside reverse transcriptase inhibitor (NRTI). Rovafovir etalafenamide is potent and active against a variety of NRTI mutants, and shows potent anti-HIV-1 activity^[1][2]. In Vitro: Rovafovir etalafenamide (GS-9131) shows anti-HIV-1 activity in PBMCs (EC₅₀=3.7 nM) and MT-2 cells (EC₅₀=150 nM). Rovafovir etalafenamide is also a potent HIV-1 inhibitor in a single-cycle infection assay with primary CD4⁺ T lymphocytes (EC₅₀=24 nM). Rovafovir etalafenamide inhibits different subtypes of HIV-1 (UG-92-031 subtype A, B940374 subtype B, LJM subtype B, BR-92-025 subtype C, and UG-92-024 subtype D) clinical isolates in PBMCs with EC₅₀s ranging from 23 to 68 nM. Rovafovir etalafenamide inhibits HIV-2 isolated in MT-2 cells (CDD77618 subtype A, CDD310248 subtype A, and CDD310319 subtype B) with EC₅₀s ranging from 39 to 650 nM^[3]. In Vivo: Rovafovir etalafenamide (GS-9131) is given orally to male beagle dogs at 3 mg/kg, it is rapidly absorbed, generating a maximum serum drug concentration (C_max) of 2.5 μM, and is subsequently eliminated from plasma with an apparent terminal half-life (t_1/2) of less than 20 min. As determined following i.v. administration, the systemic clearance of Rovafovir etalafenamide is approximately 1.4 liters/h/kg^[3].