Simeprevir (TMC435; TMC435350) sodium 是一种有效、高特异性且具有口服活性的丙型肝炎病毒 (HCV) NS3/4A蛋白酶抑制剂，Ki值为 0.36 nM，并抑制 HCV 复制，EC50值为 7.8 nM。Simeprevir sodium 还能有效抑制SARS-CoV-2的复制，并与瑞德西韦 (Remdesivir) 具有协同作用。Simeprevir sodium 可抑制 SARS-CoV-2 的主要蛋白酶 (Mpro) 和 RNA 依赖性 RNA 聚合酶 (RdRp)，并调节宿主免疫反应。
| 生物活性 | Simeprevir (TMC435; TMC435350) sodium is an oral, potent and highly specifichepatitis C virus (HCV) NS3/4A proteaseinhibitor with aKiof 0.36 nM. Simeprevir sodium inhibitsHCVreplication with anEC50of 7.8 nM. Simeprevir sodium also potently suppressesSARS-CoV-2replication and synergizes with Remdesivir. Simeprevir sodium inhibits the main protease (Mpro) and the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, and also modulates host immune responses[1][4]. |
| IC50& Target | Ki: 0.36 nM (HCV NS3/4A protease)[1]
EC50: 7.8 nM (HCV replication)[1]
IC50: 9.6±2.3 μM (SARS-CoV-2 Mpro), 5.5±0.2 μM (SARS-CoV-2 RdRp)[4] |
体外研究
(In Vitro) | Simeprevir (TMC435) inhibits HCV in a dose-dependent manner in Huh7-Luc cells, with EC50and EC90values of 8 nM and 24 nM, respectively[2].
Simeprevir (TMC435) inhibits NS3/4A proteases from HCV genotypes 1 to 6 with IC50s of 1/0.9/7/30/1.5/2.2/1.6 nM for 1a/1b/2b/3a/4/5/6, respectively[3].
Simeprevir inhibits SARS-CoV-2 in Vero E6 cells with an IC50of 9.6±2.3 μM and 5.5±0.2 μM for Mproand RdRp, respectively[4].
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体内研究
(In Vivo) | Simeprevir (TMC435) has moderate terminal elimination half-life (t1/2=1.5 h and 4.1 h for rat (3 mg/kg, p.o.), monkey (3 mg/kg, p.o.))[3].
Simeprevir (TMC435350) exhibits a medium-slow rate of absorption, well distribution with the high concentration observed in the liver, and a low clearance[1].
Pharmacokinetic Parameters of Simeprevir (TMC435350) in male Sprague-Dawley rats[1].
| IV (2 mg/kg) | PO (10 mg/kg) | | CL (L/h/kg) | 0.505 | | | Vdss(h) | 0.49 | | | AUC0-24(μM·h) | 5.21 | 2.79 | | Cmax(μM) | | 0.73 | | Tmax(h) | | 3.0 | | T1/2(h) | | 2.8 | | F (%) | | 11 | | Liver/plasma ratio at 6 h | 63.5 | 32 |
| Animal Model: | Sprague-Dawley (SD) rats and cynomolgus monkeys[3] | | Dosage: | 3 mg/kg | | Administration: | PO; single dosage | | Result: | Time at which peak concentration (Tmax) of 1 hour and 2 hour for rat and monkey, respectively.
Concentration at 24 h after dosing (C24 h) of 0.9 and 2.3 ng/mL for rat and monkey, respectively.
AUC0-24h=1173 and 1409 ng·h/mL for rat and monkey, respectively. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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