您好,欢迎来到试剂仪器网! [登录] [免费注册]
试剂仪器网
位置:首页 > 产品库 > Simeprevir
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
Simeprevir
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Simeprevir图片
CAS NO:923604-59-5
规格:≥98%
包装与价格:
包装价格(元)
1mg电议
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议
1g电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 749.94
Formula C38H47N5O7S2
CAS No. 923604-59-5; 1241946-89-3 (sodium);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 100 mg/mL (133.3 mM)
Water: < 1 mg/mL
Ethanol: 4 mg/mL (5.3 mM)
Chemical Namesodium (cyclopropylsulfonyl)((2R,3aR,11aS,12aR,14aR,Z)-2-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)-5-methyl-4,14-dioxo-1,2,3,3a,4,5,6,7,8,9,11a,12,12a,13,14,14a-hexadecahydrocyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a-carbonyl)amide
SynonymsSimeprevir; Olysio; TMC-435; TMC 435; TMC435; TMC-435350; TMC 435350; TMC435350;
SMILES CodeCOC1=C(C)C2=C(C(O[C@H]3CC(C(N(C)CCCC/C=C\[C@H](C4)[C@]4(C(NS(=O)(C5CC5)=O)=O)N6)=O)[C@H](C6=O)C3)=CC(C7=NC(C(C)C)=CS7)=N2)C=C1
实验参考方法
In Vitro

In vitro activity: the antiviral activity of simeprevir (TMC435350) in Huh7-Luc cells is dose dependent, and the EC50 and EC90 values determined for TMC435350 are 8 nM and 24 nM, respectively. Inhibition of TMC435350 on NS3/4A protease is time dependent, and the overall Kis are estimated to be 0.5 nM for genotype 1a and 0.4 nM for genotype 1b, respectively. TMC435350 is a potent inhibitor of HCV NS3/4A protease (Ki=0.36 nM) and viral replication (replicon EC50=7.8 nM).


Kinase Assay: the in vitro inhibitory activity of simeprevir against NS3/4A is determined using a fluorescence resonance energy transfer cleavage assay with the RetS1 peptide substrate, derived from the genotype 1a NS4A-4B junction, and bacterially expressed full-length NS3 protease domain, supplemented with an NS4A peptide. Briefly, NS3/4A is preincubated in the presence of TMC435350 for 10 min, and then the RetS1 substrate is added and fluorescence is continuously measured for 20 min (excitation, 355 nm; emission, 500 nm). Cleavage of the substrate is expressed as a percentage of the cleavage seen with the vehicle control.


Cell Assay: Huh7-Luc cells are seeded at a density of 2,500 cells/well in a 384-well plate in Dulbecco's modified Eagle's medium plus 10% fetal calf serum and incubated with a range of concentrations of serially diluted simeprevir (TMC435350), in a final DMSO concentration of 0.5% in the absence of G418. After 72 h of incubation, Steady Lite reagent is added in a 1:1 ratio to the medium, and luciferase signal is measured using a ViewLux reader.

In Vivo In rats, TMC435350 (40 mg/kg, p.o.) is extensively distributed to the liver and intestinal tract (tissue/plasma area under the concentration-time curve ratios of>35), and the absolute bioavailability is 44%.
Animal model 24 male specific-pathogen-free Sprague-Dawley rats, weighing between 200 and 300 g at the time of dosing, are divided into eight groups of three rats each.
Formulation & DosageDosed orally (p.o.) by gastric intubation of a vitamin E acetate-d-α-tocopheryl polyethylene glycol 1000 succinate-polyethylene glycol 400 solution of Simeprevir (TMC435350) at 2 mL/kg body weight to provide a dose of 40 mg/kg.
References Antimicrob Agents Chemother. 2009 Apr;53(4):1377-85.