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Simeprevir

现货
Catalog No.
A3820
HCV NS3/4A蛋白酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,150.00
现货
5mg
¥ 1,350.00
现货
10mg
¥ 2,150.00
现货
50mg
¥ 9,000.00
现货
100mg
¥ 14,250.00
现货

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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.

文献引用

1. Lee SH, Moon JS, et al. "HA1077 displays synergistic activity with daclatasvir against hepatitis C virus and suppresses the emergence of NS5A resistance-associated substitutions in mice." Sci Rep. 2018 Aug 20;8(1):12469. PMID:30127498

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt749.96
Cas No.923604-59-5
FormulaC38H47N5O7S2
SynonymsTMC435,TMC435350,TMC-435350,Simeprevir
Solubility≥18.75 mg/mL in DMSO, <2.52 mg/mL in EtOH, <2.25 mg/mL in H2O
SDFDownload SDF
Canonical SMILESCOC1=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
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

含HCV基因型1b复制子的Huh7-Luc细胞系

制备方法

在DMSO中的溶解度大于18.8 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

0.1 ~ 1000 nM;72小时

实验结果

在含HCV基因型1b复制子的Huh7-Luc细胞系中,Simeprevir显示出剂量依赖性的抑制作用,其EC50和EC90值分别为8 nM和24 nM。同时,Simeprevir对细胞核糖体蛋白RPL13A转录水平没有显著影响。72小时后,裂解含复制子的细胞,其免疫印迹分析结果显示,NS5B表达水平呈剂量依赖性地降低,但α-微管蛋白表达未被抑制。

动物实验 [2]:

动物模型

雄性SD大鼠

给药剂量

2 mg/kg,静脉注射或20 mg/kg,口服给药

实验结果

在雄性SD大鼠中,Simeprevir在肝脏中分布良好。口服给药后,其肝/血浆比率高达32。口服给予Simeprevir的T1/2值为2.8小时。静脉注射Simeprevir后,Simeprevir显示出较低的清除率 (Cl = 0.505 L/h/kg) 以及相应较低的Vdss (0.490 L/kg).

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

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.

质量控制

化学结构

Simeprevir

相关生物数据

Simeprevir