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Nesbuvir

现货
Catalog No.
A3655
NS5B聚合酶选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 3,030.00
现货
5mg
¥ 2,890.00
现货
10mg
¥ 4,000.00
现货
25mg
¥ 7,320.00
现货

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Background

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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt446.49
Cas No.691852-58-1
FormulaC22H23FN2O5S
SynonymsHCV 796;HCV-796;HCV796,Nesbuvir
Solubility≥22.3 mg/mL in DMSO, ≥97.8 mg/mL in EtOH with gentle warming, <2.59 mg/mL in H2O
Chemical Name5-cyclopropyl-2-(4-fluorophenyl)-6-[2-hydroxyethyl(methylsulfonyl)amino]-N-methyl-1-benzofuran-3-carboxamide
SDFDownload SDF
Canonical SMILESCNC(=O)C1=C(OC2=CC(=C(C=C21)C3CC3)N(CCO)S(=O)(=O)C)C4=CC=C(C=C4)F
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

Huh7-BB7细胞

溶解方法

在DMSO中的溶解度大于22.3 mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

7 d,40-80 nM

应用

Nesbuvir是丙型肝炎病毒非结构蛋白5B(NS5B)聚合酶的抑制剂,它可以强效特异性地抑制HCV RNA 依赖性RNA 聚合酶,从而抑制RNA的合成。在负载亚基因组基因型1b HCV复制子的Huh7-BB7细胞中,Nesbuvir和boceprevir联合使用可导致抗性变异株出现频率降低。

动物实验[2]:

动物模型

尿激酶纤溶酶原激活物(uPA)/重度联合免疫缺陷(SCID)小鼠

剂量

口服给药,50 mg/kg,每天3次,持续5天

应用

用Nesbuvir处理小鼠导致HCV滴度下降2.02 ± 0.55 log10,其中一只小鼠降到了检测水平以下,然而对照组小鼠的HCV水平相对稳定(下降0.26 ± 0.16 log10)。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

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.

生物活性

描述 Nesbuvir是HCV NS5B RNA依赖性RNA聚合酶的选择性抑制剂。
靶点 HCV NS5B RNA-dependent RNA polymerase          
IC50            

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