Simeprevir
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Simeprevir是有效的HCV NS3/4A蛋白酶抑制剂,其Ki值为0.36 nM[1]。
丙型肝炎病毒(HCV)NS3/4A蛋白酶是一种由丙型肝炎病毒编码的丝氨酸蛋白酶,裂解HCV多聚蛋白上的四个位点,在病毒复制过程中起着至关重要的作用[1]。
在Huh-7-Rep细胞中,Simeprevir抑制HCV复制,其EC50值为7.8 nM[1]。在Huh7-Luc HCV基因型1b复制子细胞系中,Simeprevir呈剂量依赖性地抑制HCV复制,其EC50和EC90值分别为8 nM和24 nM[2]。
在92例首次接受治疗的HCV基因型1感染患者中,给予Simeprevir(50或100 mg,一天一次,持续12或24周)和聚乙二醇干扰素α-2a /利巴韦林(PegIFNα-2A/RBV)(持续24或48周),或单独给予PegIFN α-2a/RBV(持续48周,PR48组),于第四周,50 mg Simeprevir联合用药组、100 mg Simeprevir联合用药组和PR48组的RNA减少量分别为-5.2、-5.2和-2.9log10 IU/mL,这表明Simeprevir可以更快地显著减少HCV RNA。此外,Simeprevir也提升病毒学应答率[3]。
参考文献:
[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-nave hepatitis C genotype 1-infected patients in Japan: the DRAGON study. J Gastroenterol, 2014, 49(1): 138-147.
- 1. Jason D Vevea, Edwin R Chapman. "Acute disruption of the synaptic vesicle membrane protein synaptotagmin 1 using knockoff in mouse hippocampal neurons." Elife. 2020;9:e56469. PMID: 32515733
- 2. 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
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 749.96 |
Cas No. | 923604-59-5 |
Formula | C38H47N5O7S2 |
Synonyms | TMC435,TMC435350,TMC-435350,Simeprevir |
Solubility | insoluble in H2O; insoluble in EtOH; ≥18.75 mg/mL in DMSO |
SDF | Download 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 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |
质量控制和MSDS
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