Oseltamivir acid  (Synonyms: GS 4071; Ro 64-0802; Oseltamivir carboxylate)

Oseltamivir acid (GS 4071), the active metabolite of Oseltamivir phosphate, is an orally bioavailable, potent and selective inhibitor of influenza virus neuraminidase (IC₅₀=2 nM) with activity against both influenza A and B viruses. Oseltamivir acid has an extremely weak ability to penetrate the BBB under normal physiological conditions, but its blood-brain barrier penetration is significantly enhanced under inflammatory conditions^{[1][2][3][4][5][6][7]}.

IC50: 2 nM (influenza virus neuraminidase)

Oseltamivir acid inhibits virus replication in vitro and in vivo. Influenza B and A/H1N1 viruses appeare to be sensitive to Oseltamivir (mean B IC₅₀ value: 13 nM; mean H1N1 IC₅₀ value: 1.34 nM), while A/H1N2 and A/H3N2 viruses are more sensitive to Oseltamivir (mean H3N2 IC₅₀ value: 0.67 nM; mean H1N2 IC₅₀ value: 0.9 nM)^[3].
In neuraminidases inhibition assays with influenza A viruses, the IC₅₀ of RWJ-270201 (approximately 0.34 nM) is comparable to that of Oseltamivir carboxylate (0.45 nM) For influenza B virus isolates, the IC₅₀ of RWJ-270201 (1.36 nM) is comparable to that of Zanamivir (2.7 nM) and less than that of Oseltamivir carboxylate (8.5 nM)^[4].

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

Oseltamivir acid (0.1, 1, or 10 mg/kg/day, twice daily by oral gavage) produces a dose-dependent antiviral effect against Vietnam/1203/04 (VN1203/04) virus. The 5-day regimen at 10 mg/kg/day protects 50% of mice; deaths in this treatment group are delayed and indicated the replication of residual virus after the completion of treatment. Dosages of 1 and 10 mg/kg/day significantly reduced virus titers in organs and provided 60% and 80% survival rates, respectively^[5].

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

284.35

C₁₄H₂₄N₂O₄

187227-45-8

Solid

White to off-white

O=C(O)C1=C[C@H]([C@@H]([C@H](C1)N)NC(C)=O)OC(CC)CC

Room temperature in continental US; may vary elsewhere.

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Li W, et al. Identification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071. Antimicrob Agents Chemother. 1998 Mar;42(3):647-53.  [Content Brief]

  [2]. Ghosh GC, et al. Oseltamivir carboxylate, the active metabolite of oseltamivir phosphate (Tamiflu), detected in sewage discharge and river water in Japan. Environ Health Perspect. 2010 Jan;118(1):103-7.  [Content Brief]

  [3]. Ferraris O, et al. Sensitivity of influenza viruses to zanamivir and oseltamivir: a study performed on viruses circulating in France prior to the introduction of neuraminidase inhibitors in clinical practice. Antiviral Res. 2005 Oct;68(1):43-8.  [Content Brief]

  [4]. Gubareva LV, et al. Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants.Antimicrob Agents Chemother. 2001 Dec;45(12):3403-8.  [Content Brief]

  [5]. Yen HL, et al. Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. J Infect Dis. 2005 Aug 15;192(4):665-72.  [Content Brief]

  [6]. Hoffmann G, et al. Nonclinical pharmacokinetics of oseltamivir and oseltamivir carboxylate in the central nervous system. Antimicrob Agents Chemother. 2009 Nov;53(11):4753-61.  [Content Brief]

  [7]. Oshima S, et al. Penetration of oseltamivir and its active metabolite into the brain after lipopolysaccharide-induced inflammation in mice. J Pharm Pharmacol. 2009 Oct;61(10):1397-400.  [Content Brief]