Simeprevir

Simeprevir is a competitive, reversible, macrocyclic, noncovalent hepatitis C virus (HCV) NS3/4A protease inhibitor that acts directly against the hepatitis C virus. It has a medium inhibitory concentration (IC50) <13 nM for all HCV NS3/4A enzymes(genotypes 1a, 1b, 2, 4, 5, and 6), but has an IC50 value of 37 nM for genotype 3.

CAS No. 923604-59-5

サイズ	価格(税別)	在庫状況
5mg	JPY 20200	国内在庫あり
25mg	JPY 58100	国内在庫あり
100mg	JPY 141600	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（6）

製品安全説明書

現在のバッチを見る：純度： 99.99%

99.99

Simeprevir関連製品

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関連化合物ライブラリー	FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Protease Inhibitor Library Ubiquitination Compound Library	もっと見る

シグナル伝達経路

HCV Proteaseシグナル伝達経路

HCV Protease阻害剤の選択性比較

生物活性

製品説明

Simeprevir is a competitive, reversible, macrocyclic, noncovalent hepatitis C virus (HCV) NS3/4A protease inhibitor that acts directly against the hepatitis C virus. It has a medium inhibitory concentration (IC50) <13 nM for all HCV NS3/4A enzymes(genotypes 1a, 1b, 2, 4, 5, and 6), but has an IC50 value of 37 nM for genotype 3.

Targets

HCV NS3/4A protease ^[1]

In Vitro
In vitro	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^[1].

In Vivo
In Vivo	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^[1].

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT03277755	Withdrawn	Hepatic Impairment	Janssen Research & Development LLC	September 11 2017	Phase 1
NCT02404805	Completed	HIV\|Hepatitis C	University of Colorado Denver	February 2016	Not Applicable
NCT02569710	Completed	Chronic Hepatitis C	Alios Biopharma Inc.	October 31 2015	Phase 2
NCT02512562	Completed	Chronic Hepatitis C	Alios Biopharma Inc.\|Alexion Pharmaceuticals Inc.	July 31 2015	Phase 1

参考
[1] Laure Izquierdo, et al. Pharmgenomics Pers Med. 2014, 7: 241-249.

参考

[1] Laure Izquierdo, et al. Pharmgenomics Pers Med. 2014, 7: 241-249.

化学情報

分子量	749.94	化学式	C₃₈H₄₇N₅O₇S₂
CAS No.	923604-59-5	SDF	--
Smiles	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
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 100 mg/mL ( (133.34 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 4 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):