Narlaprevir |
| Catalog No.GC14074 |
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 865466-24-6
Sample solution is provided at 25 µL, 10mM.
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Narlaprevir is a potent and second generation inhibitor of HCV NS3 protease with Ki value of 6 nM [1].
HCV infection is a global problem of public health. It can even cause liver cirrhosis and hepatocellular carcinoma. As an essential enzyme of HCV replication, NS3 serine protease is thought to be an attractive target for HCV infection treatment. Narlaprevir is one of the small inhibitors of NS3 protease. Unlike boceprevir, narlaprevir is a single isoform and shows improved potency. In the inhibiting process of NS3 protease, narlaprevir firstly binds the enzyme with noncovalent interactions and then binds the active-site Ser139 with a reversible covalent bond [1, 2 and 3].
In the in vitro assay, narlaprevir inhibited genotyoes 1a, 1b, 2a and 3a NS3 proteases with Ki values of 0.7, 7, 3 and 7 nM, respectively. In the virus replicon-inhibition assay, narlaprevir showed significant antiviral efficacy with EC50 and EC90 values of 20 and 40 nM, respectively. Besides that, narlaprevir had no cytotoxicity for the host cells. Narlaprevir is also used as a combination therapy with pegylated interferon. The combination treatment of narlaprevir and interferon alfa-2b showed elevated activity in replicon inhibition than the monotherapy of narlaprevir alone [2].
Narlaprevir has improved pharmacokinetic profile of both AUC and bioavailability in animal trials. It showed AUC of 6.5 μM·h, 1.1 μM·h and 0.9 μM·h in rats, monkeys and dogs, respectively. The bioavailabilities of narlaprevir in the three kinds of animals are 46%, 46% and 29%, respectively [1].
Some drug resistant mutations have been identified in the selection with high concentrations of narlaprevir, such as A156T (EC50 value of 1 μM), T54A (EC50 value of 11 nM) and the double mutation (T54A and A156T). Narlaprevir was also found to have cross-resistance to the mutations, such as V170A, F43C and V36M (EC50 value of 8 nM), which are resistant against boceprevir [2, 3].
References:
[1]. Arasappan A, Bennett F, Bogen S L, et al. Discovery of narlaprevir (SCH 900518): a potent, second generation HCV NS3 serine protease inhibitor. ACS Medicinal Chemistry Letters, 2010, 1(2): 64-69.
[2]. Tong X, Arasappan A, Bennett F, et al. Preclinical characterization of the antiviral activity of SCH 900518 (narlaprevir), a novel mechanism-based inhibitor of hepatitis C virus NS3 protease. Antimicrobial agents and chemotherapy, 2010, 54(6): 2365-2370.
[3]. Wang H, Geng L, Chen B Z, et al. Computational study on the molecular mechanisms of drug resistance of Narlaprevir due to V36M, R155K, V36M+ R155K, T54A, and A156T mutations of HCV NS3/4A protease. Biochemistry and Cell Biology, 2014, 92(5): 357-369.
| Cas No. | 865466-24-6 | SDF | |
| Chemical Name | (1R,2S,5S)-3-[(2S)-2-[[1-(tert-butylsulfonylmethyl)cyclohexyl]carbamoylamino]-3,3-dimethylbutanoyl]-N-[(3S)-1-(cyclopropylamino)-1,2-dioxoheptan-3-yl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide | ||
| Canonical SMILES | CCCCC(C(=O)C(=O)NC1CC1)NC(=O)C2C3C(C3(C)C)CN2C(=O)C(C(C)(C)C)NC(=O)NC4(CCCCC4)CS(=O)(=O)C(C)(C)C | ||
| Formula | C36H61N5O7S | M.Wt | 707.96 |
| Solubility | DMSO : ≥ 50 mg/mL (70.63 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.4125 mL | 7.0625 mL | 14.1251 mL |
| 5 mM | 0.2825 mL | 1.4125 mL | 2.825 mL |
| 10 mM | 0.1413 mL | 0.7063 mL | 1.4125 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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