| CAS NO: | 394730-60-0 |
| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 100mg | 电议 |
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 519.68 |
| Cas No. | 394730-60-0 |
| Formula | C27H45N5O5 |
| Synonyms | Boceprevir ,EBP 520;SCH 503034;EBP-520;EBP520;SCH-503034;SCH503034 |
| Solubility | ≥25.98 mg/mL in DMSO; insoluble in H2O; ≥89.8 mg/mL in EtOH |
| Chemical Name | (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 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
Boceprevir是一种有效的和选择性的丙型肝炎病毒（HCV）蛋白酶NS3抑制剂，Ki值为14 nM[1]。
丙型肝炎病毒是一种RNA病毒，感染全球约3亿人。作为HCV的丝氨酸蛋白酶，NS3在病毒进入宿主细胞后HCV的复制过程中具有重要作用。NS3可加工由病毒RNA基因组翻译而来的多聚蛋白，促进病毒的成熟。NS3也可以恢复干扰素敏感的信号通路。由于这些特点，NS3被认为是抗病毒治疗的适当靶标。SAR研究导致boceprevir（SCH 503034）的发现。Boceprevir有一个酮酰胺基，其与NS3结合形成一个共价的和可逆的加合物，具有丝氨酸活性位点[1，2和3]。
在用肝细胞所做的基于细胞的复制子实验中，boceprevir比其它衍生物具有更高的效力，IC90值为350 nM。Boceprevir的选择性通过与人嗜中性细胞弹性蛋白酶的结合而测定，其与NS3具有相似的结构。Boceprevir具有很大的选择性，HNE/HCV的比例为2200。Boceprevir比相应的氨基甲酸酯衍生物具有近15倍的选择性。在MTS实验中，该化合物在浓度高达50 μM时没有显著的细胞毒性效应[1]。
Boceprevir是一种可口服的HCV NS3蛋白酶抑制剂。在大鼠中，boceprevir口服给药具有1.5 μMH的AUC值和26%的生物利用度。在狗中，boceprevir以3 mg/kg的剂量给药具有30％的生物利用度和3.1 μMH的AUC值。Boceprevir也可与聚乙二醇干扰素（PEG-IFN-α-2B）用作联合疗法，与单独每个相比较，其联合治疗至少具有累积的效力[1，2]。
参考文献：
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.
| Cell experiment:[1] | |
Cell lines | HuH-7 cells |
Reaction Conditions | For 72 h incubation |
Applications | The EC50 and EC90 values of boceprevir on HuH-7 cells bearing the subgenomic hepatitis C virus (HCV) replicon were determined to be 0.20 μM and 0.35 μM, respectively. |
| Animal experiment:[2] | |
Animal models | NS3/4A/Lap/LC-1triple-transgenic mice induced with doxycycline |
Dosage form | 100 mg/kg Twice daily by oral gavage for 7 days |
Applications | Oral administration of boceprevir led to a 65% reduction in the average plasma Gaussia luciferase (Gluc) activity. Notably, Gluc activity gradually reverted back to the pre-treatment level when boceprevir treatment ceased. |
Note | The technical data provided above is for reference only. |
References: 1. Njoroge FG, Chen KX, Shih NY, et al. Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection. Accounts of Chemical Research, 2008, 41(1): 50-59. 2. Yao M, Lu X, Lei Y, et al. Conditional Inducible Triple-Transgenic Mouse Model for Rapid Real-Time Detection of HCV NS3/4A Protease Activity. PLoS One, 2016, 11(3): e0150894. | |
| Description | Boceprevir(EBP-520, SCH503034)是HCV蛋白酶的抑制剂，Ki值为14 nM。 | |||||
| 靶点 | HCV protease | |||||
| IC50 | 14 nM (Ki) | |||||
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