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Simeprevir

Catalog No.GC17270

A potent NS3/4A protease inhibitor

Products are for research use only. Not for human use. We do not sell to patients.

Simeprevir Chemical Structure

Cas No.: 923604-59-5

Taille Prix Stock Qté
10mM (in 1mL DMSO)
161,00 $US
En stock
5mg
90,00 $US
En stock
10mg
135,00 $US
En stock
50mg
405,00 $US
En stock
100mg
675,00 $US
En stock
500mg
1 500,00 $US
En stock
1g
2 400,00 $US
En stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Cell experiment [1]:

Cell lines

Huh7-Luc HCV genotype 1b replicon cell line

Preparation method

The solubility of this compound in DMSO is > 18.8 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

0.1 ~ 1000 nM; 72 hrs

Applications

In Huh7-Luc HCV genotype 1b replicon cell line, Simeprevir exhibited dose-dependent inhibitory effects, with the EC50 and EC90 values of 8 nM and 24 nM, respectively. Meanwhile, Simeprevir did not show significant effect on the cellular ribosomal protein RPL13A transcript level. According to the immunoblot analysis of replicon cell lysates collected after 72 hrs, NS5B expression was dose-dependently reduced, but α-tubulin expression was not suppressed.

Animal experiment [2]:

Animal models

Male SD rats

Dosage form

2 mg/kg, i.v. or 20 mg/kg, p.o.

Applications

In male SD rats, Simeprevir was well distributed in the liver, with a high liver/plasma ratio after oral administration reaching 32. The T1/2 value for oral administration of Simeprevir was 2.8 hrs. When Simeprevir was given intravenously, Simeprevir showed a low clearance (Cl = 0.505 L/h/kg) associated with a low Vdss (0.490 L/kg).

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]. Lin TI, Lenz O, Fanning G, et al. In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor. Antimicrob Agents Chemother, 2009, 53(4): 1377-1385.

[2]. Raboisson P, de Kock H, Rosenquist A, et al. Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett, 2008, 18(17): 4853-4858.

Background

Simeprevir is a potent inhibitor of HCV NS3/4A protease with Ki value of 0.36 nM [1].
The hepatitis C virus (HCV) NS3/4A protease is a serine protease encoded by HCV and is responsible for cleavage at four sites of the HCV polyprotein. It is essential for viral replication [1].
In Huh-7-Rep cells, Simeprevir inhibited HCV replication with EC50 of 7.8 nM [1]. In the Huh7-Luc HCV genotype 1b replicon cell line, Simeprevir inhibited HCV replication with EC50 and EC90 values of 8 nM and 24 nM respectively in a dose dependent way [2].
In ninety-two naive, HCV genotype 1-infected patients, treatment with Simeprevir (50 or 100 mg QD) for 12 or 24 weeks and peginterferon α-2a/ribavirin (PegIFNα-2a/RBV) for 24 or 48 weeks or PegIFN α-2a/RBV for 48 weeks lonely (PR48 group), RNA reductions in the 4 week were -5.2,-5.2 and-2.9 log10IU/mL for Simeprevir 50 mg combined, 100 mg combined and PR48 groups, respectively, which suggested Simeprevir reduced HCV RNA more rapidly and substantially. Also, Simeprevir increased the virologic response rates [3].
References:
[1]. Raboisson P, de Kock H, Rosenquist A, et al. Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett, 2008, 18(17): 4853-4858.
[2]. Lin TI, Lenz O, Fanning G, et al. In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor. Antimicrob Agents Chemother, 2009, 53(4): 1377-1385.
[3]. Hayashi N, Seto C, Kato M, et al. Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naïve hepatitis C genotype 1-infected patients in Japan: the DRAGON study. J Gastroenterol, 2014, 49(1): 138-147.

Chemical Properties

Cas No. 923604-59-5 SDF
Canonical SMILES COC1=CC=C(C(O[C@H]2CC(C(N(C)CCCC/C=C\[C@H]3C[C@@]3(C(NS(=O)(C4CC4)=O)=O)NC5=O)=O)[C@H]5C2)=CC(C6=NC(C(C)C)=CS6)=N7)C7=C1C
Formula C38H47N5O7S2 M.Wt 749.96
Solubility ≥ 18.75 mg/mL in DMSO 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.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 1.3334 mL 6.667 mL 13.334 mL
5 mM 0.2667 mL 1.3334 mL 2.6668 mL
10 mM 0.1333 mL 0.6667 mL 1.3334 mL
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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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3. All of the above co-solvents are available for purchase on the GlpBio website.

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Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

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