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Nesbuvir

In stock
Catalog No.
A3655
NS5B polymerase inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$326.00
In stock
5mg
$297.00
In stock
10mg
$411.00
In stock
25mg
$770.00
In stock

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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
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment[1]:

Cell lines

Huh7-BB7 cells

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.

Reacting condition

7 d, 40-80 nM

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]:

Animal models

Urokinase plasminogen activator (uPA)/severe combined immunodeficient (SCID) mice

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).

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.

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.

Biological Activity

Description Nesbuvir is a selective inhibitor of HCV NS5B RNA-dependent RNA polymerase.
Targets HCV NS5B RNA-dependent RNA polymerase          
IC50            

Quality Control

Chemical structure

Nesbuvir