Ombitasvir (ABT-267)
(Synonyms: 奥比他韦; ABT-267) 目录号 : GC33914
A hepatitis C virus NS5A inhibitor
Cas No.:1258226-87-7
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
Ombitasvir is an orally bioavailable and potent inhibitor of the hepatitis C virus (HCV) non-structural protein 5A (NS5A).1,2 It reduces HCV replication in stable replicon cell lines with EC50 values ranging from 0.82 to 19.3 pM against genotypes 1a, 1b, 2a, 2b, 3a, 4a, and 5a and an EC50 value of 366 pM for genotype 6a.1,2 Against subgenomic replicons from clinical isolates of genotypes 1a-6a expressed in Huh-7 derived cells, ombitasvir inhibits HCV replication with EC50 values ranging from 0.1 pM for genotype 4a to 68 pM for genotype 6a.2 Formulations containing ombitasvir have been used in the treatment of HCV genotypes 1 and 4.
1.Zhang, X.Direct anti-HCV agentsActa Pharmaceutica Sinica B6(1)26-31(2015) 2.Krishnan, P., Beyer, J., Mistry, N., et al.In vitro and in vivo antiviral activity and resistance profile of ombitasvir, an inhibitor of hepatitis C virus NS5AAntimicrob. Agents Chemother.59(2)979-987(2015)
| Cas No. | 1258226-87-7 | SDF | |
| 别名 | 奥比他韦; ABT-267 | ||
| Canonical SMILES | CC(C)(C)C(C=C1)=CC=C1N2[C@H](C3=CC=C(NC([C@H]4N(C([C@@H](NC(OC)=O)C(C)C)=O)CCC4)=O)C=C3)CC[C@H]2C5=CC=C(NC([C@@H]6CCCN6C([C@@H](NC(OC)=O)C(C)C)=O)=O)C=C5 | ||
| 分子式 | C50H67N7O8 | 分子量 | 894.11 |
| 溶解度 | DMSO : ≥ 33 mg/mL (36.91 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 | 1.1184 mL | 5.5922 mL | 11.1843 mL |
| 5 mM | 0.2237 mL | 1.1184 mL | 2.2369 mL |
| 10 mM | 0.1118 mL | 0.5592 mL | 1.1184 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。
Ombitasvir (ABT-267), a novel NS5A inhibitor for the treatment of hepatitis C
Expert Opin Pharmacother 2014 Dec;15(17):2609-22.PMID:25347030DOI:10.1517/14656566.2014.972364.
Introduction: Chronic hepatitis C infection is a global disease with 160 million people infected worldwide. Until recently, therapy was characterized by long duration, suboptimal success rates and significant adverse drug reactions. The development of direct-acting antivirals initiated a dramatic change in the treatment of hepatitis C. Areas covered: This review covers the development of the novel NS5A inhibitor Ombitasvir (ABT-267) and its clinical evaluation in Phase I to III trials as monotherapy and in combination with the NS3/4A inhibitor ABT-450/r and the non-nucleoside NS5B inhibitor dasabuvir (ABT-333) ± ribavirin. Expert opinion: Ombitasvir (ABT-267) is a potent inhibitor of the hepatitis C virus protein NS5A, has favorable pharmacokinetic characteristics and is active in the picomolar range against genotype 1 - 6. In patients with genotype 1 and 4, 12-week combination treatment with ombitasvir, dasabuvir and ABT-450/r plus ribavirin was highly effective and resulted in 12-week sustained virological response rates higher than 95% in treatment-naöve and treatment-experienced patients. In liver transplant recipients with genotype 1 hepatitis C, success rates in the same range can be expected after 24 weeks of treatment according to preliminary trial results. Genotype 1a patients with compensated cirrhosis who were prior nonresponders benefit from a treatment duration of 24 weeks.
ABT-450/ ritonavir and ABT-267 in combination with ABT-333 for the treatment of hepatitis C virus
Expert Opin Pharmacother 2015 Apr;16(6):929-37.PMID:25800085DOI:10.1517/14656566.2015.1024653.
Introduction: The global prevalence of chronic hepatitis C virus (HCV) is estimated to be 80 - 115 million and currently viremic infections account for 350,000 deaths annually. As the knowledge about HCV evolves, new anti-viral treatments have been developed. The primary goal of antiviral therapies has been to eradicate HCV virus from serum and achieve sustained virologic response (SVR). Historically, interferon has been a staple of nearly all HCV treatment regimens, despite significant toxic effects. Areas covered: In recent years, HCV treatment has changed rapidly and significantly. All-oral treatment regimens show promise for treatment with shorter duration and more manageable side effects. New antivirals aimed at improving SVR may provide a cure to nearly all HCV-infected patients. The unique combination of ABT-450 (paritaprevir) and ABT-267 (Ombitasvir) provides highly effective treatment for patients with genotype 1 HCV. This review will examine the antiviral properties, pharmacokinetics, pharmacodynamics, and side effects of these agents. Expert opinion: The combination of ABT-450/r and ABT-267 has improved potency, favorable side effect profile, and low risk of resistance compared to the first-generation protease inhibitors. This combination is likely to be a major part of novel upcoming HCV treatment regimens and is likely to be widely used by clinicians. Additional data is awaited in additional patient populations, and with possible shorter treatment durations.
Diagnosis and Management of Hepatitis C
Am Fam Physician 2015 Jun 15;91(12):835-42.PMID:26131943doi
Hepatitis C virus (HCV) infection, a major cause of chronic liver disease and cirrhosis, is predominantly transmitted by exposure to blood or body fluids. The infection progresses to a chronic state in 80% of patients, whereas the virus clears completely after the acute infection in 20% of patients. Screening for HCV with an anti-HCV antibody test is recommended for all adults at high risk of infection, and one-time screening is recommended in adults born between 1945 and 1965. If the anti-HCV antibody test result is positive, current infection should be confirmed with a qualitative HCV RNA test. In patients with confirmed HCV infection, quantitative HCV RNA testing and testing for HCV genotype is recommended. An assessment of the degree of liver fibrosis with liver biopsy or noninvasive testing is necessary to determine the urgency of treatment. Treatment of patients with chronic HCV infection should be considered based on genotype, extent of fibrosis or cirrhosis, prior treatment, comorbidities, and potential adverse effects. The goal of therapy is to reduce all-cause mortality and liver-associated complications. Although interferon-based regimens have been the mainstay of treatment for HCV infection, the U.S. Food and Drug Administration recently approved two combination-pill interferon-free treatments (ledipasvir plus sofosbuvir, and Ombitasvir/paritaprevir/ritonavir plus dasabuvir) for chronic HCV genotype 1.
ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV
N Engl J Med 2014 May 22;370(21):1983-92.PMID:24795200DOI:10.1056/NEJMoa1402338.
Background: The interferon-free regimen of ABT-450 with ritonavir (ABT-450/r), Ombitasvir, and dasabuvir with or without ribavirin has shown efficacy in inducing a sustained virologic response in a phase 2 study involving patients with hepatitis C virus (HCV) genotype 1 infection. We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. Methods: We randomly assigned 419 patients with HCV genotype 1b infection (PEARL-III study) and 305 patients with genotype 1a infection (PEARL-IV study) to 12 weeks of ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of Ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight or to matching placebo for ribavirin. The primary efficacy end point was a sustained virologic response (an HCV RNA level of <25 IU per milliliter) 12 weeks after the end of treatment. Results: The study regimen resulted in high rates of sustained virologic response among patients with HCV genotype 1b infection (99.5% with ribavirin and 99.0% without ribavirin) and among those with genotype 1a infection (97.0% and 90.2%, respectively). Of patients with genotype 1b infection, 1 had virologic failure, and 2 did not have data available at post-treatment week 12. Among patients with genotype 1a infection, the rate of virologic failure was higher in the ribavirin-free group than in the ribavirin group (7.8% vs. 2.0%). In both studies, decreases in the hemoglobin level were significantly more common in patients receiving ribavirin. Two patients (0.3%) discontinued the study drugs owing to adverse events. The most common adverse events were fatigue, headache, and nausea. Conclusions: Twelve weeks of treatment with ABT-450/r-ombitasvir and dasabuvir without ribavirin was associated with high rates of sustained virologic response among previously untreated patients with HCV genotype 1 infection. Rates of virologic failure were higher without ribavirin than with ribavirin among patients with genotype 1a infection but not among those with genotype 1b infection. (Funded by AbbVie; PEARL-III and PEARL-IV ClinicalTrials.gov numbers, NCT01767116 and NCT01833533.).
ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis
N Engl J Med 2014 May 22;370(21):1973-82.PMID:24725237DOI:10.1056/NEJMoa1402869.
Background: Interferon-containing regimens for the treatment of hepatitis C virus (HCV) infection are associated with increased toxic effects in patients who also have cirrhosis. We evaluated the interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the NS5A inhibitor Ombitasvir (ABT-267), the nonnucleoside polymerase inhibitor dasabuvir (ABT-333), and ribavirin in an open-label phase 3 trial involving previously untreated and previously treated adults with HCV genotype 1 infection and compensated cirrhosis. Methods: We randomly assigned 380 patients with Child-Pugh class A cirrhosis to receive either 12 or 24 weeks of treatment with ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight. The primary efficacy end point was a sustained virologic response 12 weeks after the end of treatment. The rate of sustained virologic response in each group was compared with the estimated rate with a telaprevir-based regimen (47%; 95% confidence interval [CI], 41 to 54). A noninferiority margin of 10.5 percentage points established 43% as the noninferiority threshold; the superiority threshold was 54%. Results: A total of 191 of 208 patients who received 12 weeks of treatment had a sustained virologic response at post-treatment week 12, for a rate of 91.8% (97.5% CI, 87.6 to 96.1). A total of 165 of 172 patients who received 24 weeks of treatment had a sustained virologic response at post-treatment week 12, for a rate of 95.9% (97.5% CI, 92.6 to 99.3). These rates were superior to the historical control rate. The three most common adverse events were fatigue (in 32.7% of patients in the 12-week group and 46.5% of patients in the 24-week group), headache (in 27.9% and 30.8%, respectively), and nausea (in 17.8% and 20.3%, respectively). The hemoglobin level was less than 10 g per deciliter in 7.2% and 11.0% of patients in the respective groups. Overall, 2.1% of patients discontinued treatment owing to adverse events. Conclusions: In this phase 3 trial of an oral, interferon-free regimen evaluated exclusively in patients with HCV genotype 1 infection and cirrhosis, multitargeted therapy with the use of three new antiviral agents and ribavirin resulted in high rates of sustained virologic response. Drug discontinuations due to adverse events were infrequent. (Funded by AbbVie; TURQUOISE-II ClinicalTrials.gov number, NCT01704755.).