Sofosbuvir

Sofosbuvir is a pivotal antiviral pharmaceutical intermediate and active pharmaceutical ingredient (API) used in the treatment of chronic hepatitis C virus infection. As a nucleotide analog prodrug, Sofosbuvir is metabolized intracellularly to the active antiviral agent 2′-deoxy-2′-α-fluoro-β-C-methyluridine-5′-monophosphate (GS-461203), which acts as a chain terminator during HCV RNA replication. The clinical success of Sofosbuvir has established it as the backbone of multiple highly effective direct-acting antiviral (DAA) combination therapies, including the fixed-dose combinations with ledipasvir, velpatasvir, and voxilaprevir. In quality control contexts, Sofosbuvir is subject to stringent impurity profiling, with reference standards available for process-related impurities such as Sofosbuvir Impurity M, Impurity A, and various diastereoisomeric impurities. As a critical reference standard for analytical method development and validation, Sofosbuvir and its related impurities are indispensable for ensuring the purity, safety, and efficacy of sofosbuvir-containing drug products in ANDA filings and commercial manufacturing.

 

Product Parameters

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Parameter	Specification
Product Name	Sofosbuvir
CAS Number	1190307-88-0
Molecular Formula	C₂₂H₂₉FN₃O₉P
Molecular Weight	529.45 g/mol
Appearance	White to off-white solid
Melting Point	122–124 °C
Density	1.41 g/cm³
pKa	9.39 ± 0.10
Storage Condition	Hygroscopic, –20 °C, under inert atmosphere

Application

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Sofosbuvir is a prodrug that can be metabolized into the active antiviral agent 2 '-deoxy-2' -α-fluoro-β-C-methyluridine-5'-monophosphate and is currently undergoing Phase III clinical trials according to Chemicalbook for the treatment of hepatitis C. Studies have demonstrated that sofosbuvir acts as a nucleotide inhibitor of the hepatitis C virus, exhibiting selective inhibition of HCV NS5B polymerase.

 

Bioactivity

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Sofosbuvir (PSI-7977, GS-7977) is an HCV NS5B polymerase inhibitor used for the treatment of chronic hepatitis C virus (HCV) infection.

 

In Vitro S tudy

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As an HCV NS5B polymerase inhibitor, PSI-7977 exhibits greater efficacy than PSI-7976 in inhibiting HCV RNA replication, with EC50 values of 92 nM and 1.07 μM, respectively, and EC90 values of 0.29 μM and 2.99 μM, respectively. When incubated with PSI-7977, clone A cells produced higher concentrations of PSI-7409 compared to those incubated with PSI-7976. PSI-7977 serves as an effective substrate for CatA, forming PSI-352707, which demonstrates over 30-fold greater potency than PSI-7976. The S282T NS5B mutant exhibits reduced susceptibility to PSI-7977, with its EC90 value increasing from 0.42 μM to 7.8 μM. In eight-day cytotoxicity assays, PSI-7977 showed no cytotoxic effects on Huh7, HepG2, BxPC3, or CEM cells even at concentrations up to 100 μM. After 14 days of treatment, PSI-7977 significantly inhibited mtDNA and rDNA replication in HepG2 cells, with IC90 values of 72.1 μM and 68.6 μM, respectively. PSI-7977 effectively suppresses replication in genotype (GT) 1a,1b, and 2a, as well as in chimeric replication involving NS5B polymerases with GT 2a,2b, or 3a. Sequence analysis of the JFH-1NS5B region demonstrated that other amino acid substitutions occurring around the S282T mutation site—including T179A, M289L, I293L, M434T, and H479P—are essential for resistance to PSI-7977.

 

Contact Us

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Need Sofosbuvir for your HCV antiviral manufacturing campaign, impurity profiling program, or analytical method development? Cosperpharm makes it straightforward. Contact our team today to discuss your requirements, request a quote, or schedule a quality audit.