Boceprevir
(Synonyms: 波普瑞韦; EBP 520; SCH 503034) 目录号 : GC10959An NS3/4A protease inhibitor
Sample solution is provided at 25 µL, 10mM.
Animal experiment: | Mice[2] Boceprevir is purchased from MedChem Express. To evaluate the effect of Boceprevir, triple-transgenic mice are induced with Doxycycline (Dox) for 10 days (n=5 per group). On the third day after Dox induction, when plasma Gluc activity reaches its peak, the mice are administered either Boceprevir (100 mg/kg) or DMSO via oral gavage twice daily for 7 days. During this period, blood is collected from the caudal vein daily to detect plasma Gluc activity. |
References: [1]. Njoroge FG, et al. Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection. Acc Chem Res. 2008 Jan;41(1):50-9. |
Boceprevir is a potent and selective inhibitor of hepatitis C virus (HCV) protease NS3 with Ki value of 14 nM [1].
HCV is a type of RNA virus and infects about 300 million people worldwide. As a serine protease of HCV, NS3 plays an important role in the replication process of HCV when the virus enters the host cell. NS3 processes the polyprotein translated from the virus RNA genome and promotes the maturation of the virus. NS3 is also found to restore the interferon-sensitive signaling pathway. Due to these features, NS3 is thought to be the appropriate target for the therapy of antivirus. The SAR studies led to the discovery of boceprevir (also named as SCH 503034). Boceprevir has a ketoamide group, it binds NS3 and forms a covalent and reversible adduct with the active site serine [1, 2 and 3].
In the cell-based replicon assay using hepatocytes, boceprevir showed improved potency than other derivatives with IC90 value of 350 nM. The selectivity of boceprevir was tested by binding to human neutrophil elastase which had similar structure with NS3. Boceprevir exerted a great selectivity with a HNE/HCV ratio of 2200. It is approximately 15-fold more selective than the corresponding carbamate derivative. In MTS assay, the compound showed no significant cytotoxicity even when its concentration was up to 50 μM [1].
Boceprevir is an orally bioavailable inhibitor of HCV NS3 protease. In rats, oral administration of boceprevir showed AUC value of 1.5 μM•H and bioavailability of 26%. In dogs, boceprevir demonstrated a 30% bioavailability with AUC value of 3.1μM•H at a dose of 3 mg/kg. Boceprevir was also used as a combination therapy with the pegylated interferon (PEG-IFN-α-2B). It was found that the combination showed at least addictive potency compared with each one alone [1, 2].
References:
1.Venkatraman S, Bogen S L, Arasappan A, et al. Discovery of (1 R, 5 S)-N-[3-Amino-1-(cyclobutylmethyl)-2, 3-dioxopropyl]-3-[2 (S)-[[[(1, 1-dimethylethyl) amino] carbonyl] amino]-3, 3-dimethyl-1-oxobutyl]-6, 6-dimethyl-3-azabicyclo [3.1. 0] hexan-2 (S)-carboxamide (SCH 503034), a Selective, Potent, Orally Bioavailable Hepatitis C Virus NS3 Protease Inhibitor: A Potential Therapeutic Agent for the Treatment of Hepatitis C Infection. Journal of medicinal chemistry, 2006, 49(20): 6074-6086.
2.Sarrazin C, Rouzier R, Wagner F, et al. SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon α-2b for genotype 1 nonresponders. Gastroenterology, 2007, 132(4): 1270-1278.
3.Flores M V, Strawbridge J, Ciaramella G, et al. HCV-NS3 inhibitors: determination of their kinetic parameters and mechanism. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 2009, 1794(10): 1441-1448.
Cas No. | 394730-60-0 | SDF | |
别名 | 波普瑞韦; EBP 520; SCH 503034 | ||
化学名 | (1R,2S,5S)-N-(4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-[(2S)-2-(tert-butylcarbamoylamino)-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide | ||
Canonical SMILES | CC1(C2C1C(N(C2)C(=O)C(C(C)(C)C)NC(=O)NC(C)(C)C)C(=O)NC(CC3CCC3)C(=O)C(=O)N)C | ||
分子式 | C27H45N5O5 | 分子量 | 519.68 |
溶解度 | ≥ 25.98 mg/mL in DMSO, ≥ 89.8 mg/mL in EtOH | 储存条件 | Store at -20°C, protect from light, stored under nitrogen |
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. | ||
Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方) | ||||||||||
% DMSO % % Tween 80 % ddH2O | ||||||||||
计算重置 |
计算结果:
工作液浓度: mg/ml;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL ddH2O,混匀澄清。
1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
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