Simeprevir

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的口服 HCV NS3/4A 蛋白酶抑制剂，Ki 为 0.36 nM，复制子 EC50 为 7.8 nM。

A potent, orally available inhibitor of HCV NS3/4A protease with Ki of 0.36 nM, replicon EC50 of 7.8 nM; inhibits NS3/4A proteases of genotypes 1a and 1b with Ki of 0.5 and 0.4 nM, shows synergistic effect with α-Interferon and an NS5B inhibitor in the replicon model and additive with ribavirin; exerts favorable pharmacokinetic profile and antiviral activity in vivo.HCV Infection Approved(In Vitro):Simeprevir (TMC435) inhibits HCV in a dose-dependent manner in Huh7-Luc cells, with EC50 and EC90 values of 8 nM and 24 nM, respectively.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.Simeprevir inhibits SARS-CoV-2 in Vero E6 cells with IC50s of 9.6±2.3 μM and 5.5±0.2 μM for Mpro and RdRp, respectively.(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.)).Simeprevir (TMC435350) exhibits a medium-slow rate of absorption, well distribution with the high concentration observed in the liver, and a low clearance.

Simeprevir (TMC435) inhibits HCV in a dose-dependent manner in Huh7-Luc cells, with EC50 and EC90 values of 8 nM and 24 nM, respectively.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.Simeprevir inhibits SARS-CoV-2 in Vero E6 cells with IC50s of 9.6±2.3 μM and 5.5±0.2 μM for Mpro and RdRp, respectively.

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.)).Simeprevir (TMC435350) exhibits a medium-slow rate of absorption, well distribution with the high concentration observed in the liver, and a low clearance.Pharmacokinetic Parameters of Simeprevir (TMC435350) in male Sprague-Dawley rats.Animal Model:Sprague-Dawley (SD) rats and cynomolgus monkeys Dosage:3 mg/kg Administration:Oral administration 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 and1409 ng ? h/mL for rat and monkey, respectively.

TMC-435 | TMC435 | TMC435350 | TMC-435350

Microbiology/Virology

HCV

HCV

Infection

HCV Infection

923604-59-5

749.9391

C38H47N5O7S2

>98% (HPLC)

10 mM in DMSO

CC1=C(C=CC2=C1N=C(C=C2OC3CC4C(C3)C(=O)N(CCCCC=CC5CC5(NC4=O)C(=O)NS(=O)(=O)C6CC6)C)C7=NC(=CS7)C(C)C)OC

Cyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a(1H)-carboxamide, N-(cyclopropylsulfonyl)-2,3,3a,4,5,6,7,8,9,11a,12,13,14,14a-tetradecahydro-2-[[7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]-4-quinolinyl]oxy]-5-methyl-4,14-dioxo-, (2R,3aR,1

(-20℃)

With Ice Pack

≥ 2 years