Simeprevir (TMC435)

Simeprevir (TMC435) 
分子式:C38H47N5O7S2 分子量:749.94

简介: Simeprevir一种竞争性的、可逆的、非共价结合的大环hepatitis C virus (HCV) NS3/4A protease抑制剂,直接抑制HCV病毒。它对HCV NS3/4A(genotypes 1a, 1b, 2, 4, 5, and 6)的平均IC50值小于13 nM,而对genotype 3的IC50值为37 nM。 
溶解性:…………………H2O : Insoluble ;DMSO:100 mg/mL (133.34 mM);Ethanol:4 mg/mL (5.33 mM) 



Simeprevir一种竞争性的、可逆的、非共价结合的大环hepatitis C virus (HCV) NS3/4A protease抑制剂,直接抑制HCV病毒。它对HCV NS3/4A(genotypes 1a, 1b, 2, 4, 5, and 6)的平均IC50值小于13 nM,而对genotype 3的IC50值为37 nM。

IC50 & Target

HCV NS3/4A protease



Simeprevir exhibits potent inhibition on NS3/4A protease of genotypes 1a, 1b, 2, 4, 5, and 6, with a medium inhibitory concentration (IC50) <13 nM for all HCV NS3/4A enzymes tested. However, the IC50 for genotype 3 is 37 nM. In vitro, simeprevir is also an inhibitor of bilirubin transporters OATP1B1 and MRP2. It is a more potent inhibitor of OATP1B1 (IC50=720 nM), which is primarily responsible for transporting unconjugated bilirubin, than MRP2 (IC50 around 10,000 nM), primarily a conjugated bilirubin transporter


In vivo, simeprevir has a relatively long absorption phase, reaching maximum concentration (Cmax) after 4-6 hours. It is extensively (99.9%) bound to plasma proteins, mainly to albumin. The absolute bioavailability is 44% after a single oral administration. In rats, The liver to blood ratio is 29:1, which means good distribution to the liver. For humans, in preclinical studies, the liver to plasma concentration ratio is really high (ratio of 39). The highest tissue/plasma AUC ratios are observed in the small intestine (ratio of 128). While tissue simeprevir concentrations reaches peak values within 4 hours postdosing, simeprevir concentrations in liver remains above the EC99 for up to 31 hours postdosing, and plasma concentrations are higher than the EC99 at 8 hours and around the EC50 at 24 hours postdosing. The AUC24h of simeprevir is increased by 61%-69% when administered with food. Simeprevir should therefore be taken with food. Simeprevir is also a substrate and inhibitor of P-glycoprotein. Simeprevir is metabolized by CYP3A4 and eliminated by biliary excretion. It is also an inhibitor of gut cytochrome 3A4 but not hepatic CYP3A4.

储液配置及储存: 按表中溶解性配置;如溶解困难,可以通过快速搅拌,超声或温和加热(在45-60°C下水浴)。液体稳定性报道的很少,建议现配现用,如需储存,建议:-20℃1-3月;-80℃ 3-6月。


1 mg

5 mg

10 mg

1 mM

1.3334 mL

6.6672 mL

13.3344 mL

5 mM

0.2667 mL

1.3334 mL

2.6669 mL

10 mM

0.1333 mL

0.6667 mL

1.3334 mL

50 mM

0.0267 mL

0.1333 mL

0.2667 mL




CAS 号:923604-59-5
英文名字:Simeprevir (TMC435)