Voxilaprevir
(Synonyms: 伏西瑞韦; GS-9857) 目录号 : GC37921
A pan-genotypic HCV NS3/4A protease inhibitor
Cas No.:1535212-07-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Voxilaprevir is a pan-genotypic hepatitis C virus (HCV) non-structural 3/4A (NS3/4A) serine protease inhibitor.1 It inhibits replication of wild-type HCV genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, and 6a (EC50s = 1.9-6.6 nM in replicon assays). Voxilaprevir also inhibits replication of mutant HCV genotypes containing NS3 resistance-associated substitutions (EC50s = 3.1, 2.7, and 4 nM for HCV genotypes 1a Q80K, 1a R155K, and 1b D168E, respectively). Formulations containing voxilaprevir have been used in the treatment of chronic HCV infection.
1.Taylor, J.G., Zipfel, S., Ramey, K., et al.Discovery of the pan-genotypic hepatitis C virus NS3/4A protease inhibitor voxilaprevir (GS-9857): A component of Vosevi?Bioorg. Med. Chem. Lett.29(16)2428-2436(2019)
| Cas No. | 1535212-07-7 | SDF | |
| 别名 | 伏西瑞韦; GS-9857 | ||
| Canonical SMILES | O=C([C@H]1N(C([C@@H](NC(O[C@H]2[C@H]3C2)=O)C(C)(C)C)=O)C[C@@](OC4=NC5=CC(OC)=CC=C5N=C4C(F)(CCCC3)F)([H])[C@H]1CC)N[C@]6([C@H](C(F)F)C6)C(NS(=O)(C7(CC7)C)=O)=O | ||
| 分子式 | C40H52F4N6O9S | 分子量 | 868.93 |
| 溶解度 | DMSO : ≥ 100 mg/mL (115.08 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.1508 mL | 5.7542 mL | 11.5084 mL |
| 5 mM | 0.2302 mL | 1.1508 mL | 2.3017 mL |
| 10 mM | 0.1151 mL | 0.5754 mL | 1.1508 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection
N Engl J Med 2017 Jun 1;376(22):2134-2146.PMID:28564569DOI:10.1056/NEJMoa1613512.
Background: Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options. Methods: We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor Voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks. Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir-voxilaprevir (163 patients) or sofosbuvir-velpatasvir (151 patients) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. Results: In the three active-treatment groups, 46% of the patients had compensated cirrhosis. In POLARIS-1, the rate of sustained virologic response was 96% with sofosbuvir-velpatasvir-voxilaprevir, as compared with 0% with placebo. In POLARIS-4, the rate of response was 98% with sofosbuvir-velpatasvir-voxilaprevir and 90% with sofosbuvir-velpatasvir. The most common adverse events were headache, fatigue, diarrhea, and nausea. In the active-treatment groups in both trials, the percentage of patients who discontinued treatment owing to adverse events was 1% or lower. Conclusions: Sofosbuvir-velpatasvir-voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed. (Funded by Gilead Sciences; POLARIS-1 and POLARIS-4 ClinicalTrials.gov numbers, NCT02607735 and NCT02639247 .).
Profile of sofosbuvir/velpatasvir/Voxilaprevir in the treatment of hepatitis C
Infect Drug Resist 2019 Jul 23;12:2259-2268.PMID:31413603DOI:10.2147/IDR.S171338.
The treatment of chronic hepatitis C has been revolutionized with the introduction of direct-acting antivirals (DAAs). However, some patients are not cured with first-line treatment. Sofosbuvir/velpatasvir/Voxilaprevir is a fixed-dose combination of a polymerase inhibitor, an NS5A inhibitor, and a protease inhibitor with activity against strains of the hepatitis C virus that show resistance to other first-line antiviral regimens. Sofosbuvir/velpatasvir/Voxilaprevir has been studied in four Phase III randomized trials: POLARIS-1, -2, -3, and -4, which enrolled both treatment naïve and experienced patients with and without compensated cirrhosis. In these trials, at least 95% of patients treated with sofosbuvir/velpatasvir/Voxilaprevir achieved sustained virological response (SVR). This includes favorable treatment outcomes in patients who had previously failed a regimen containing sofosbuvir or an NS5A inhibitor. Patient-reported outcomes also improved during and after treatment with sofosbuvir/velpatasvir/Voxilaprevir. Treatment with sofosbuvir/velpatasvir/Voxilaprevir is well tolerated, with the most commonly reported adverse events being headache, fatigue, diarrhea, and nausea. The approval of sofosbuvir/velpatasvir/Voxilaprevir allows a treatment option for patients who have failed treatment with certain DAA regimens.
Sofosbuvir/Velpatasvir/Voxilaprevir: A Pan-Genotypic Direct-Acting Antiviral Combination for Hepatitis C
Ann Pharmacother 2018 Apr;52(4):352-363.PMID:29115151DOI:10.1177/1060028017741508.
Objectives: To review the efficacy and safety of sofosbuvir/velpatasvir/Voxilaprevir in the treatment of hepatitis C virus (HCV) infection. Data sources: A literature search through PubMed was conducted (August 2010 to August 2017) using the terms GS-9857, Voxilaprevir, and NS3/4A protease inhibitor. Study selection/data extraction: Studies of sofosbuvir/velpatasvir/Voxilaprevir were identified. Data synthesis: Sofosbuvir/velpatasvir/Voxilaprevir is indicated for adult patients with chronic HCV without cirrhosis or with compensated cirrhosis who have (1) genotype 1 through 6 and have previously been treated with an NS5A inhibitor or (2) genotype 1a or 3 and have previously been treated with sofosbuvir without an NS5A inhibitor. POLARIS-1 demonstrated that sofosbuvir/velpatasvir/Voxilaprevir for 12 weeks was highly effective in patients with HCV genotype 1 through 6 who had prior exposure to an NS5A inhibitor. POLARIS-2 failed to demonstrate that sofosbuvir/velpatasvir/Voxilaprevir for 8 weeks was noninferior to sofosbuvir/velpatasvir for 12 weeks in patients with HCV genotype 1 through 6 who had no prior exposure to direct-acting antivirals (DAAs). POLARIS-3 demonstrated that sofosbuvir/velpatasvir/Voxilaprevir for 8 weeks was as effective as sofosbuvir/velpatasvir for 12 weeks in patients with HCV genotype 3 and compensated cirrhosis who had no prior exposure to DAAs. POLARIS-4 demonstrated that sofosbuvir/velpatasvir/Voxilaprevir was as effective as sofosbuvir/velpatasvir for 12 weeks in patients with HCV genotype 1 through 3 who had prior exposure to DAAs but not an NS5A inhibitor. The most common adverse reactions were headache, fatigue, diarrhea, and nausea. Conclusions: Sofosbuvir/velpatasvir/Voxilaprevir is safe and effective to treat HCV in patients who have previously been treated with DAAs.
Sofosbuvir/Velpatasvir/Voxilaprevir: A Review in Chronic Hepatitis C
Drugs 2018 Apr;78(5):577-587.PMID:29546556DOI:10.1007/s40265-018-0895-5.
A fixed-dose combination of the hepatitis C virus (HCV) NS5B polymerase inhibitor sofosbuvir, the HCV NS5A inhibitor velpatasvir and the HCV NS3/4A protease inhibitor Voxilaprevir (sofosbuvir/velpatasvir/Voxilaprevir; Vosevi®) is approved in the EU for the treatment of chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection in adults. In the phase III POLARIS trials, in patients who had HCV genotype 1-6 infection with or without compensated cirrhosis, overall rates of sustained virological response at 12 weeks post-treatment (SVR12) with sofosbuvir/velpatasvir/Voxilaprevir were high after 8 weeks of treatment in direct-acting antiviral (DAA)-naïve patients and 12 weeks of treatment in DAA-experienced patients. However, 8 weeks of sofosbuvir/velpatasvir/Voxilaprevir was inferior to 12 weeks of sofosbuvir/velpatasvir in cirrhotic or non-cirrhotic DAA-naïve patients with HCV genotype 1, 2, 4, 5 or 6 infection and non-cirrhotic DAA-naïve patients with HCV genotype 3 infection, mostly due to an insufficient treatment period. Sofosbuvir/velpatasvir/Voxilaprevir was generally well tolerated, with most adverse events being of mild or moderate intensity. The most common adverse events included headache, fatigue, nausea and diarrhoea. In conclusion, sofosbuvir/velpatasvir/Voxilaprevir is an important and effective option for the treatment of HCV genotype 1-6 infection in adults, especially those who have previously failed a DAA therapy with or without an HCV NS5A inhibitor.
Sofosbuvir/velpatasvir/Voxilaprevir: a highly effective option for retreatment of hepatitis C in difficult-to-treat patients
Antivir Ther 2019;24(1):1-10.PMID:30210057DOI:10.3851/IMP3264.
Treatment for hepatitis C has escalated rapidly since the advent of direct-acting antivirals. Although there are highly efficacious, pangenotypic regimens available as standard of care, 5-10% of patients do not achieve virological cure. The recently approved fixed-dose combination of sofosbuvir, velpatasvir and Voxilaprevir provides an option for retreatment in patients who have failed prior regimens and have characteristics which make them difficult to treat. This review provides a summary of the evidence for use of Vosevi®, a fixed-dose combination pill for treatment of hepatitis C in treatment-experienced patients.