Nesbuvir
(Synonyms: 5-环丙基-2-(4-氟苯基)-6-[(2-羟基乙基)(甲基磺酰基)氨基]-N-甲基-3-苯并呋喃甲酰胺,HCV 796;HCV-796;HCV796,Nesbuvir ) 目录号 : GC15891
Nesbuvir 是丙型肝炎病毒 (HCV) 非结构蛋白 5B (NS5B) 聚合酶的非核苷抑制剂。
Cas No.:691852-58-1
Sample solution is provided at 25 µL, 10mM.
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Nesbuvir is a novel selective inhibitor of nonstructural protein 5B (NS5B) polymerase with IC50 value of 5 nM [1].
NS5B (nonstructural protein 5B) is a viral protein found in HCV and plays an important role in HCV RNA replicate by using the viral positive RNA strand as its template and catalyzing the polymerization of rNTP during RNA replication. As the principal catalytic enzyme for HCV replication, NS5B is a viable target for HCV-RNA replication and used as a target for HCV therapy [2] [3].
Nesbuvir is a selective NS5B polymerase inhibitor and has a different selectivity with the reported ALK inhibitor crizotinib. When tested with Huh7.5 cell line, nesbuvir showed the highest selectivity for NS5B and mutations reduced the cells susceptibility [1]. In Clone A cells derived from Huh-7 cells containing approximately 1,000 genome copies of HCV genotype 1b replicon per cell, nesbuvir treatment with the concentration of 0.1 and 1 μM for 16-day reduced about 3.6 log10 and 4.2 log10 HCV RNA levels, respectively [2].
In the chimeric mouse model, nesbuvir treatment resulted in a 2.02 +/- 0.55 log reduction in HCV titer, whereas in combination with interferon using a suboptimal dose of 30 mg/kg three times per day showed a 2.44 log reduction and were better than interferon treatment only [4].
References:
[1]. Flint, M., et al., Selection and characterization of hepatitis C virus replicons dually resistant to the polymerase and protease inhibitors HCV-796 and boceprevir (SCH 503034). Antimicrob Agents Chemother, 2009. 53(2): p. 401-11.
[2]. Howe, A.Y., et al., Molecular mechanism of hepatitis C virus replicon variants with reduced susceptibility to a benzofuran inhibitor, HCV-796. Antimicrob Agents Chemother, 2008. 52(9): p. 3327-38.
[3]. Meshram, R.J. and R.N. Gacche, Effective epitope identification employing phylogenetic, mutational variability, sequence entropy, and correlated mutation analysis targeting NS5B protein of hepatitis C virus: from bioinformatics to therapeutics. J Mol Recognit, 2015.
[4]. Kneteman, N.M., et al., HCV796: A selective nonstructural protein 5B polymerase inhibitor with potent anti-hepatitis C virus activity in vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus. Hepatology, 2009. 49(3): p. 745-52.
| Cell experiment[1]: | |
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Cell lines |
Huh7-BB7 cells |
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Preparation method |
The solubility of this compound in DMSO is > 22.3 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
7 d, 40-80 nM |
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Applications |
Nesbuvir is an inhibitor of the hepatitis C virus （HCV）nonstructural protein 5B (NS5B) polymerase. It has potent and specific inhibitory effect against the HCV RdRp, thus inhibiting RNA synthesis. When Nesbuvir is used in combination with boceprevir, it decreases the frequency with which resistant variants occur in Huh7-BB7 cells bearing a subgenomic genotype 1b HCV replicon. |
| Animal experiment [2]: | |
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Animal models |
Urokinase plasminogen activator (uPA)/severe combined immunodeficient (SCID) mice |
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Dosage form |
Oral administration, 50 mg/kg，three times daily for 5 days |
|
Application |
Treating mice with Nesbuvir resulted in a 2.02 ± 0.55 log10 decrease of HCV titer with one mouse below the level of detection, whereas HCV levels in the control group of mice were relatively stable (0.26 ± 0.16 log10 decline). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Flint M, Mullen S, Deatly A M, et al. Selection and characterization of hepatitis C virus replicons dually resistant to the polymerase and protease inhibitors HCV-796 and boceprevir (SCH 503034)[J]. Antimicrobial agents and chemotherapy, 2009, 53(2): 401-411. [2]. Kneteman N M, Howe A Y M, Gao T, et al. HCV796: a selective nonstructural protein 5B polymerase inhibitor with potent anti‐hepatitis C virus activity in vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus[J]. Hepatology, 2009, 49(3): 745-752. | |
| Cas No. | 691852-58-1 | SDF | |
| 别名 | 5-环丙基-2-(4-氟苯基)-6-[(2-羟基乙基)(甲基磺酰基)氨基]-N-甲基-3-苯并呋喃甲酰胺,HCV 796;HCV-796;HCV796,Nesbuvir | ||
| 化学名 | 5-cyclopropyl-2-(4-fluorophenyl)-6-[2-hydroxyethyl(methylsulfonyl)amino]-N-methyl-1-benzofuran-3-carboxamide | ||
| Canonical SMILES | CNC(=O)C1=C(OC2=CC(=C(C=C21)C3CC3)N(CCO)S(=O)(=O)C)C4=CC=C(C=C4)F | ||
| 分子式 | C22H23FN2O5S | 分子量 | 446.49 |
| 溶解度 | ≥ 22.3 mg/mL in DMSO, ≥ 97.8 mg/mL in EtOH with gentle warming | 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 | 2.2397 mL | 11.1985 mL | 22.3969 mL |
| 5 mM | 0.4479 mL | 2.2397 mL | 4.4794 mL |
| 10 mM | 0.224 mL | 1.1198 mL | 2.2397 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet