Rovafovir etalafenamide  (Synonyms: GS-9131)

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].

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

506.42

C₂₁H₂₄FN₆O₆P

912809-27-9

Solid

White to off-white

FC([C@](O1)([H])N2C3=NC=NC(N)=C3N=C2)=C[C@H]1OC[P@](OC4=CC=CC=C4)(N[C@@H](C)C(OCC)=O)=O

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Mackman RL, et al. Discovery of GS-9131: Design, synthesis and optimization of amidate prodrugs of the novel nucleoside phosphonate HIV reverse transcriptase (RT) inhibitor GS-9148. Bioorg Med Chem. 2010;18(10):3606‐3617.  [Content Brief]

  [2]. Rai MA, Pannek S, Fichtenbaum CJ. Emerging reverse transcriptase inhibitors for HIV-1 infection. Expert Opin Emerg Drugs. 2018;23(2):149‐157.  [Content Brief]

  [3]. Cihlar T, et al. Design and profiling of GS-9148, a novel nucleotide analog active against nucleoside-resistant variants of human immunodeficiency virus type 1, and its orally bioavailable phosphonoamidate prodrug, GS-9131. Antimicrob Agents Chemother. 2008;52(2):655‐665.  [Content Brief]