	Sofosbuvir is a direct-acting antiviral agent (pan-genotypic polymerase inhibitor) against the hepatitis C virus. HCV RNA replication is mediated by a membrane-associated multiprotein replication complex. The HCV polymerase (NS5B protein) is an RNA-dependent RNA polymerase (RdRp). It is the essential initiating and catalytic subunit of this replication complex and is critical for the viral replication cycle. There is no human homolog for HCV NS5B RdRp. Sofosbuvir is a monophosphorylated pyrimidine nucleotide prodrug that undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203). GS-461203 competes with natural nucleotides for incorporation (by HCV NS5B) into the nascent RNA strand during replication of the viral genome. GS-461203 differs from endogenous pyrimidine nucleotides in that it has been modified at the 2' position with the addition of a methyl and a fluoro functional group. Incorporation of GS-461203 into nascent RNA strongly reduces the efficiency of further RNA elongation by RdRp, resulting in premature termination of RNA synthesis. The stopping of viral replication leads to a rapid decline of HCV viral load and clearing of HCV levels in the body.
CAS 编号	1190307-88-0
分子式	C22H29FN3O9P
分子量	529.5 g/mol
IUPAC 名称	propan-2-yl 2-[[[(4R)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
InChI	InChI=1S/C22H29FN3O9P/c1-13(2)33-19(29)14(3)25-36(31,35-15-8-6-5-7-9-15)32-12-16-18(28)22(4,23)20(34-16)26-11-10-17(27)24-21(26)30/h5-11,13-14,16,18,20,28H,12H2,1-4H3,(H,25,31)(H,24,27,30)/t14?,16?,18?,20?,22-,36+/m1/s1
InChI 键	TTZHDVOVKQGIBA-IECBXEDQSA-N
SMILES	CC(C)OC(=O)C(C)NP(=O)(OCC1C(C(C(O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3
手性 SMILES	CC(C)OC(=O)C(C)N[P@](=O)(OCC1C([C@@](C(O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3
规范 SMILES	CC(C)OC(=O)C(C)NP(=O)(OCC1C(C(C(O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3
外观	white solid powder
颜色/形态	White to off-white crystalline solid
纯度	>98% (or refer to the Certificate of Analysis)
保质期	>2 years if stored properly
溶解度	Slightly soluble in water
储存	Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
同义词	PSI-7977; PSI 7977; PSI7977; GS7977; GS-7977; GS 7977; Sofosbuvir; Sovaldi; Virunon; Vosevi; Hepcinat; Hepcvir; Resof;
产品来源	United States

Customer

Q & A

Q1: What is the mechanism of action of Sofosbuvir?

A1: Sofosbuvir is a pan-genotypic inhibitor of the Hepatitis C Virus (HCV) NS5B RNA polymerase, a key enzyme responsible for viral replication. [, , , , , ] It acts as a chain-terminating nucleotide analogue, interfering directly with the HCV life cycle by suppressing viral replication. [, , ]

Q2: How does Sofosbuvir affect HCV after binding to NS5B polymerase?

A2: Upon entering hepatocytes (liver cells), Sofosbuvir is metabolized into its active form, a nucleoside triphosphate. This active metabolite competes with naturally occurring nucleotides, ultimately leading to the termination of RNA chain elongation during HCV replication. [, ]

Q3: What is the molecular formula and weight of Sofosbuvir?

A3: The scientific literature provided does not specify the exact molecular formula and weight of Sofosbuvir.

Q4: How stable is Sofosbuvir under various storage conditions?

A5: While specific stability data is limited in the provided research, Sofosbuvir has been successfully formulated into tablets for oral administration. [, , , , , ] Stability indicating HPTLC methods have been developed for Sofosbuvir and Daclatasvir in combination, highlighting the need for validated methods to assess drug stability. []

Q5: Does Sofosbuvir have any catalytic properties?

A5: Sofosbuvir itself doesn't possess catalytic properties. Its antiviral action stems from inhibiting the catalytic activity of the HCV NS5B polymerase.

Q6: Have any computational studies been conducted on Sofosbuvir?

A6: There is no mention of specific computational chemistry studies on Sofosbuvir within the provided research articles.

Q7: What formulation strategies have been explored for Sofosbuvir?

A9: Sofosbuvir is primarily formulated as tablets for oral administration. [, , , , , ] Further research exploring strategies to optimize Sofosbuvir formulation for improved stability, solubility, and bioavailability is warranted.

Q8: Is there information regarding Sofosbuvir's SHE compliance?

A8: The provided scientific research focuses primarily on the clinical efficacy and safety of Sofosbuvir. Information regarding specific SHE (Safety, Health, and Environment) regulations and compliance is not discussed.

Q9: What is known about the pharmacokinetic profile of Sofosbuvir?

A11: Sofosbuvir is readily absorbed after oral administration, achieving peak plasma concentrations in approximately 30 minutes. [, ] It undergoes extensive hepatic metabolism, primarily by phosphorylation, into its active triphosphate form. [, , ] The primary metabolite, GS-331007, is largely inactive against HCV and is eliminated in the urine. []

Q10: What cell-based assays have been used to evaluate Sofosbuvir's activity?

A13: Sofosbuvir's antiviral activity has been extensively studied in cell culture using HCV replicons. [, , ] These replicons are engineered systems that allow for the replication of the HCV genome in cultured cells, enabling the assessment of antiviral activity. Resistance selection experiments have also been conducted in cell culture to understand the emergence of resistance to Sofosbuvir. []

Q11: What is the efficacy of Sofosbuvir in clinical trials?

A14: Clinical trials have demonstrated that Sofosbuvir-based regimens achieve high sustained virological response (SVR) rates, signifying viral eradication, across various HCV genotypes and patient populations. [, , , , , , , , , , , , , , ] Notably, Sofosbuvir-containing regimens have shown efficacy in treatment-naïve and treatment-experienced patients, as well as in those with cirrhosis. [, , , , , , , , , , , , , , ]

Q12: What are the primary mechanisms of resistance to Sofosbuvir?

A15: The primary mechanism of Sofosbuvir resistance involves mutations in the NS5B polymerase, specifically the S282T substitution. This mutation has been identified across all HCV genotypes and confers reduced susceptibility to Sofosbuvir. [, , ]

Q13: Does cross-resistance occur between Sofosbuvir and other antivirals?

A16: While S282T is the primary resistance mutation, other substitutions in NS5B can emerge during Sofosbuvir treatment, and their impact on resistance and cross-resistance with other antivirals requires further investigation. [] Clinical studies have shown that Sofosbuvir-containing regimens, particularly Sofosbuvir/Velpatasvir/Voxilaprevir, are effective as salvage therapies in patients who have failed prior DAA treatments. []

Q14: Are there any specific drug delivery strategies for Sofosbuvir?

A17: The provided research primarily focuses on the oral formulation and efficacy of Sofosbuvir. [, , , , , ] Specific drug delivery and targeting strategies for Sofosbuvir are not discussed in detail within these articles.

Q15: Are there any biomarkers associated with Sofosbuvir treatment response?

A18: The research primarily focuses on sustained virologic response (SVR) as the primary indicator of Sofosbuvir treatment efficacy. [, , , , , , , , , , , , , , ] The research does not delve into specific biomarkers to predict treatment response or identify potential adverse effects.

Q16: What analytical methods are used to quantify Sofosbuvir?

A19: Several analytical techniques have been employed for Sofosbuvir quantification, including high-performance liquid chromatography (HPLC) and UV spectrophotometry. [, , , , , ] Stability indicating HPTLC methods have also been developed to assess Sofosbuvir stability. []

Q17: Are there specific methods for analyzing Sofosbuvir in biological samples?

A17: The provided research does not delve into specific details regarding the analysis of Sofosbuvir in biological samples.

Q18: What is the environmental impact of Sofosbuvir?

A18: The provided research focuses on the clinical aspects of Sofosbuvir, and information regarding its environmental impact and degradation is not discussed.

Q19: What quality control measures are in place for Sofosbuvir manufacturing?

A19: Specific quality control and assurance measures implemented during Sofosbuvir development, manufacturing, and distribution are not discussed in detail in the provided research.

Q20: Does Sofosbuvir elicit any immune responses?

A20: The provided scientific literature primarily focuses on the antiviral efficacy and safety profile of Sofosbuvir. Information concerning its potential immunogenicity and effects on immunological responses is not discussed.

Q21: Does Sofosbuvir interact with drug transporters?

A26: Preliminary research suggests that genetic variants in drug transporter genes like ABCB1 might affect Sofosbuvir's primary metabolite concentration. [] This highlights the need for further investigation into potential drug-transporter interactions.

Q22: Does Sofosbuvir affect drug-metabolizing enzymes?

A22: The provided research focuses on Sofosbuvir's interaction with HCV and its clinical efficacy. It doesn't detail its impact on drug-metabolizing enzyme activity.

Q23: What is known about the biocompatibility of Sofosbuvir?

A23: The primary focus of the research is Sofosbuvir's clinical effectiveness and safety in treating HCV. Specific details regarding its biocompatibility and biodegradability are not discussed.

Q24: Are there any alternative therapies to Sofosbuvir-based regimens for HCV?

A29: The landscape of HCV treatment has evolved significantly with the advent of direct-acting antivirals (DAAs). [, , , , , , ] Prior to DAAs, the standard of care involved interferon-based therapies, which were associated with significant side effects and lower efficacy. [, , , , , ] Sofosbuvir, as a highly effective DAA, has largely replaced interferon-based therapies as the preferred treatment option for most patients.

Q25: Are there strategies for recycling or managing Sofosbuvir waste?

A25: The research provided does not offer information on Sofosbuvir waste management or recycling strategies.

Q26: What research tools and resources have been crucial in Sofosbuvir research?

A26: While not explicitly stated, the research highlights the use of several key tools and resources, including:

HCV replicons: Essential for evaluating Sofosbuvir's antiviral activity and resistance profiling. [, , ]
Clinical trial networks: Collaborative efforts across multiple research centers were crucial for conducting large-scale clinical trials. [, , , , , , , , , , , , , , ]
Analytical techniques: Methods like HPLC and UV spectrophotometry are vital for Sofosbuvir quantification and stability studies. [, , , , , ]

Q27: What were the major milestones in the development of Sofosbuvir?

A27: Key milestones in Sofosbuvir's development include:

Clinical trials: Successful completion of Phase 2 and 3 clinical trials demonstrating high SVR rates across HCV genotypes. [, , , , , , , , , , , , , , ]
Regulatory approval: FDA approval of Sofosbuvir in 2013, marking a significant advancement in HCV treatment. [, ]
Real-world effectiveness: Continued evaluation of Sofosbuvir's efficacy and safety in broader patient populations. [, ]

Q28: How has Sofosbuvir research fostered cross-disciplinary collaborations?

A28: The development of Sofosbuvir has spurred collaborations across various scientific disciplines, including:

Virology and Molecular Biology: Understanding HCV replication mechanisms and resistance pathways. [, , ]
Medicinal Chemistry and Pharmacology: Designing, synthesizing, and evaluating the drug's pharmacokinetic and pharmacodynamic properties. [, , , , ]
Clinical Medicine and Hepatology: Conducting clinical trials, evaluating efficacy and safety, and managing HCV-infected patients. [, , , , , , , , , , , , , , ]
Analytical Chemistry: Developing and validating methods for Sofosbuvir quantification and quality control. [, , , , , ]

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