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。
物理性状及指标：
外观：……………………粉末
溶解性：…………………H2O : Insoluble ；DMSO：100 mg/mL (133.34 mM)；Ethanol：4 mg/mL (5.33 mM)
含量：……………………>98%
储存温度：-20℃，避光防潮密闭干燥
生物活性
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描述 |
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。 |
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IC50 & Target |
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体外 |
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 |
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体内 |
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。
| 浓度/体积/质量 |
1 mg |
5 mg |
10 mg |
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1 mM |
1.3334 mL |
6.6672 mL |
13.3344 mL |
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5 mM |
0.2667 mL |
1.3334 mL |
2.6669 mL |
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10 mM |
0.1333 mL |
0.6667 mL |
1.3334 mL |
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50 mM |
0.0267 mL |
0.1333 mL |
0.2667 mL |
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