Simeprevir
(Synonyms: 西咪匹韦; TMC435; TMC435350) 目录号 : GC17270
A potent NS3/4A protease inhibitor
Cas No.:923604-59-5
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment [1]: | |
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Cell lines |
Huh7-Luc HCV genotype 1b replicon cell line |
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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. |
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Reacting condition |
0.1 ~ 1000 nM; 72 hrs |
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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]: | |
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Animal models |
Male SD rats |
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Dosage form |
2 mg/kg, i.v. or 20 mg/kg, p.o. |
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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). |
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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. |
|
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. |
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| Cas No. | 923604-59-5 | SDF | |
| 别名 | 西咪匹韦; TMC435; TMC435350 | ||
| 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 | ||
| 分子式 | C38H47N5O7S2 | 分子量 | 749.96 |
| 溶解度 | ≥ 18.75 mg/mL in DMSO | 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 | |||
 |
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 |
| 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet